16-30729012-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006662.3(SRCAP):c.5705A>G(p.Glu1902Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0055 in 1,614,090 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1902Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 39 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.18

Publications

11 publications found

Variant links:

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Floating-Harbor syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SRCAP links:

ENSG00000282034 (HGNC:):

ENSG00000282034 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009796977).

BP6

Variant 16-30729012-A-G is Benign according to our data. Variant chr16-30729012-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0039 (594/152226) while in subpopulation NFE AF = 0.00616 (419/68012). AF 95% confidence interval is 0.00567. There are 2 homozygotes in GnomAd4. There are 291 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRCAP	NM_006662.3 link	c.5705A>G	p.Glu1902Gly	missense_variant	Exon 26 of 34	ENST00000262518.9	NP_006653.2	Q6ZRS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9 link	c.5705A>G	p.Glu1902Gly	missense_variant	Exon 26 of 34	2	NM_006662.3	ENSP00000262518.4		Q6ZRS2-1
ENSG00000282034	ENST00000380361.7 link	n.5174A>G		non_coding_transcript_exon_variant	Exon 21 of 31	2		ENSP00000369719.3		A0A0C4DFX4

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

594

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00396

AC:

995

AN:

251408

AF XY:

0.00401

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00915

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00567

AC:

8282

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

3943

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00127

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00122

AC:

105

AN:

86256

European-Finnish (FIN)

AF:

0.00884

AC:

472

AN:

53420

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00657

AC:

7302

AN:

1111988

Other (OTH)

AF:

0.00487

AC:

294

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

501

1003

1504

2006

2507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152226

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41552

American (AMR)

AF:

0.00262

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00166

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00801

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00616

AC:

419

AN:

68012

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00500

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00399

AC:

484

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 19, 2017

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BS1,BS2,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, was seen in a healthy adult where full penetrance of the disorder is expected at an early age, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 19, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SRCAP: BP4, BS1, BS2 -

Floating-Harbor syndrome

Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

0.069

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.0098

T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.69

N;.

PhyloP100

4.2

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.9

D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.10

T;T

Polyphen

0.36

B;.

Vest4

0.48

MVP

0.26

MPC

0.73

ClinPred

0.020

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.48

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over