Variant 16-30700876-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006662.3(SRCAP):c.52C>G(p.Gln18Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SRCAP
NM_006662.3 missense, splice_region

Scores

Splicing: ADA: 0.9258

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07355508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRCAP	NM_006662.3 link	c.52C>G	p.Gln18Glu	missense_variant, splice_region_variant	Exon 3 of 34	ENST00000262518.9	NP_006653.2	Q6ZRS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRCAP	ENST00000262518.9 link	c.52C>G	p.Gln18Glu	missense_variant, splice_region_variant	Exon 3 of 34	2	NM_006662.3	ENSP00000262518.4	Q6ZRS2-1
SRCAP	ENST00000411466.7 link	c.52C>G	p.Gln18Glu	missense_variant, splice_region_variant	Exon 3 of 34	3		ENSP00000405186.3	Q6ZRS2-1C9J4U4
SRCAP	ENST00000706321.1 link	c.52C>G	p.Gln18Glu	missense_variant, splice_region_variant	Exon 3 of 34			ENSP00000516346.1	Q6ZRS2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248758

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Uncertain:1

May 08, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.041

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.13

Sift

Benign

0.13

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0020

.;B

Vest4

0.18

MutPred

0.19

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.082

MPC

0.011

ClinPred

0.25

GERP RS

4.1

Varity_R

0.24

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Benign

0.51

SpliceAI score (max)

0.070

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