rs149217909

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.8755C>T(p.Leu2919Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,918 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 3.00

Publications

5 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
Floating-Harbor syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

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=0.010218084).

BP6

Variant 16-30738795-C-T is Benign according to our data. Variant chr16-30738795-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 160039.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 = 0.00131 (200/152326) while in subpopulation NFE AF = 0.00216 (147/68034). AF 95% confidence interval is 0.00188. There are 1 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 200 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.8755C>T	p.Leu2919Phe	missense	Exon 34 of 34	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.8755C>T	p.Leu2919Phe	missense	Exon 34 of 34	ENSP00000262518.4	Q6ZRS2-1
ENSG00000282034	ENST00000380361.7	TSL:2	n.8224C>T		non_coding_transcript_exon	Exon 29 of 31	ENSP00000369719.3	A0A0C4DFX4
SRCAP	ENST00000411466.7	TSL:3	c.8755C>T	p.Leu2919Phe	missense	Exon 34 of 34	ENSP00000405186.3	C9J4U4

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00119

AC:

299

AN:

250968

AF XY:

0.00124

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00217

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00175

AC:

2554

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1260

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33478

American (AMR)

AF:

0.000783

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000487

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00210

AC:

2333

AN:

1111886

Other (OTH)

AF:

0.00171

AC:

103

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

183

367

550

734

917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00131

AC:

200

AN:

152326

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41566

American (AMR)

AF:

0.00176

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00216

AC:

147

AN:

68034

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

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:

0.00193

Hom.:

Bravo

AF:

0.00154

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00135

AC:

164

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00243

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (7)

Floating-Harbor syndrome;C5562012:Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (1)

Inborn genetic diseases (1)

not specified (1)

SRCAP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.046

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.79

M_CAP

Benign

0.063

MetaRNN

Benign

0.010

MetaSVM

Uncertain

-0.047

MutationAssessor

Benign

0.81

PhyloP100

3.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Benign

0.28

Sift

Uncertain

0.013

Sift4G

Benign

0.12

Polyphen

0.57

Vest4

0.14

MVP

0.33

MPC

0.19

ClinPred

0.024

GERP RS

2.4

Varity_R

0.089

gMVP

0.042

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over