rs117480926

Positions:

chr16-30729012-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_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 (★★).

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

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 links:

ENSG00000282034 (HGNC:):

ENSG00000282034 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SRCAP. . Gene score misZ 2.1272 (greater than the threshold 3.09). Trascript score misZ 3.6253 (greater than threshold 3.09). GenCC has associacion of gene with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome.

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 [Likely_benign]. Clinvar id is 260020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30729012-A-G is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3 linkuse as main transcript	c.5705A>G	p.Glu1902Gly	missense_variant	26/34	ENST00000262518.9	NP_006653.2	Q6ZRS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9 linkuse as main transcript	c.5705A>G	p.Glu1902Gly	missense_variant	26/34	2	NM_006662.3	ENSP00000262518.4		Q6ZRS2-1
ENSG00000282034	ENST00000380361.7 linkuse as main transcript	n.5174A>G		non_coding_transcript_exon_variant	21/31	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

GnomAD3 exomes

AF:

0.00396

AC:

995

AN:

251408

Hom.:

AF XY:

0.00401

AC XY:

545

AN XY:

135880

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 SAS exome

AF:

0.00124

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

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00884

Gnomad4 NFE exome

AF:

0.00657

Gnomad4 OTH exome

AF:

0.00487

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152226

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00546

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

Benign, criteria provided, single submitter	clinical testing	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	Apr 19, 2017	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 19, 2015	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	SRCAP: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Floating-Harbor syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over