rs79597785

Positions:

• chr16-30723717-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006662.3(SRCAP):​c.4293C>G​(p.Val1431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,614,130 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (29 hom., cov: 32)
  • Exomes 𝑓: 0.023 (503 hom.)
• Consequence: SRCAP NM_006662.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.426

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-30723717-C-G is Benign according to our data. Variant chr16-30723717-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 160034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.426 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2231/152244) while in subpopulation NFE AF= 0.0246 (1673/68020). AF 95% confidence interval is 0.0236. There are 29 homozygotes in gnomad4. There are 996 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3	c.4293C>G	p.Val1431=	synonymous_variant	25/34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9	c.4293C>G	p.Val1431=	synonymous_variant	25/34	2	NM_006662.3	ENSP00000262518	P1
SRCAP	ENST00000411466.7	c.4293C>G	p.Val1431=	synonymous_variant	25/34	3		ENSP00000405186	P1
SRCAP	ENST00000706321.1	c.4293C>G	p.Val1431=	synonymous_variant	25/34			ENSP00000516346	P1
SRCAP	ENST00000483083.3	c.3393C>G	p.Val1131=	synonymous_variant	18/18	2		ENSP00000483329

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2232 AN: 152126 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.0130 AC: 3280 AN: 251474 Hom.: 47 AF XY: 0.0132 AC XY: 1791 AN XY: 135908

Gnomad AFR exome AF: 0.00412

Gnomad AMR exome AF: 0.00761

Gnomad ASJ exome AF: 0.00883

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00222

Gnomad FIN exome AF: 0.00360

Gnomad NFE exome AF: 0.0231

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.0231 AC: 33703 AN: 1461886 Hom.: 503 Cov.: 35 AF XY: 0.0223 AC XY: 16238 AN XY: 727244

Gnomad4 AFR exome AF: 0.00343

Gnomad4 AMR exome AF: 0.00803

Gnomad4 ASJ exome AF: 0.00914

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00232

Gnomad4 FIN exome AF: 0.00455

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0147 AC: 2231 AN: 152244 Hom.: 29 Cov.: 32 AF XY: 0.0134 AC XY: 996 AN XY: 74444

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.0193 Hom.: 8

Bravo AF: 0.0149

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0193

EpiControl AF: 0.0229

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	See Variant Classification Assertion Criteria. -
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 29, 2024	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 04, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs79597785; hg19: chr16-30735038;