rs149248373

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3302C>A(p.Thr1101Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,613,894 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. T1101M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0056 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 57 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.28

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=0.0060519874).

BP6

Variant 16-30721237-C-A is Benign according to our data. Variant chr16-30721237-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260017.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 = 0.00562 (856/152290) while in subpopulation NFE AF = 0.00866 (589/68020). AF 95% confidence interval is 0.00808. There are 5 homozygotes in GnomAd4. There are 401 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 856 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRCAP	NM_006662.3 link	c.3302C>A	p.Thr1101Lys	missense_variant	Exon 21 of 34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9 link	c.3302C>A	p.Thr1101Lys	missense_variant	Exon 21 of 34	2	NM_006662.3	ENSP00000262518.4
ENSG00000282034	ENST00000380361.7 link	n.3196+259C>A		intron_variant	Intron 17 of 30	2		ENSP00000369719.3

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

857

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00867

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00554

AC:

1382

AN:

249334

AF XY:

0.00529

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00561

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00524

Gnomad NFE exome

AF:

0.00919

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00750

AC:

10967

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

5231

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33478

American (AMR)

AF:

0.00309

AC:

138

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00652

AC:

170

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000626

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00669

AC:

357

AN:

53352

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00883

AC:

9818

AN:

1111904

Other (OTH)

AF:

0.00636

AC:

384

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

743

1487

2230

2974

3717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.00562

AC:

856

AN:

152290

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

401

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41552

American (AMR)

AF:

0.00667

AC:

102

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00556

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00866

AC:

589

AN:

68020

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00572

Hom.:

Bravo

AF:

0.00570

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00600

AC:

729

EpiCase

AF:

0.00698

EpiControl

AF:

0.00800

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SRCAP: BP4, BS1, BS2 -

not specified

Benign:2

Aug 31, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.30

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.14

N;.

PhyloP100

1.3

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

N;.

REVEL

Uncertain

0.34

Sift

Benign

0.039

D;.

Sift4G

Benign

0.34

T;T

Polyphen

0.48

P;.

Vest4

0.47

MVP

0.52

MPC

0.65

ClinPred

0.0072

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.26

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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