16-30721237-C-A

Position:

chr16-30721237-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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=0.0060519874).

BP6

Variant 16-30721237-C-A is Benign according to our data. Variant chr16-30721237-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 260017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30721237-C-A is described in Lovd as [Likely_benign].

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

BS2

High AC in GnomAd4 at 856 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3 linkuse as main transcript	c.3302C>A	p.Thr1101Lys	missense_variant	21/34	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.3302C>A	p.Thr1101Lys	missense_variant	21/34	2	NM_006662.3	ENSP00000262518.4		Q6ZRS2-1
ENSG00000282034	ENST00000380361.7 linkuse as main transcript	n.3196+259C>A		intron_variant		2		ENSP00000369719.3		A0A0C4DFX4

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

GnomAD3 exomes

AF:

0.00554

AC:

1382

AN:

249334

Hom.:

AF XY:

0.00529

AC XY:

713

AN XY:

134840

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 SAS exome

AF:

0.000655

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

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00652

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.00669

Gnomad4 NFE exome

AF:

0.00883

Gnomad4 OTH exome

AF:

0.00636

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152290

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

401

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.00866

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00585

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

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	SRCAP: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 31, 2016	- -

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

0.30

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

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;.

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

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

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