rs149628651

Positions:

• chr16-30704141-C-T

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.132C>T​(p.Gly44Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,186 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (6 hom.)
• Consequence: SRCAP NM_006662.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.189

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]

ENSG00000282034 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 16-30704141-C-T is Benign according to our data. Variant chr16-30704141-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.189 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00181 (275/152296) while in subpopulation NFE AF= 0.003 (204/68026). AF 95% confidence interval is 0.00266. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 275 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3	c.132C>T	p.Gly44Gly	synonymous_variant	4/34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9	c.132C>T	p.Gly44Gly	synonymous_variant	4/34	2	NM_006662.3	ENSP00000262518.4
ENSG00000282034	ENST00000380361.7	n.75C>T		non_coding_transcript_exon_variant	1/31	2		ENSP00000369719.3
SRCAP	ENST00000411466.7	c.132C>T	p.Gly44Gly	synonymous_variant	4/34	3		ENSP00000405186.3
SRCAP	ENST00000706321.1	c.132C>T	p.Gly44Gly	synonymous_variant	4/34			ENSP00000516346.1

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 275 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00161 AC: 401 AN: 249558 Hom.: 1 AF XY: 0.00164 AC XY: 222 AN XY: 135396

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000649

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00191 AC: 2799 AN: 1461890 Hom.: 6 Cov.: 31 AF XY: 0.00191 AC XY: 1389 AN XY: 727244

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000973

Gnomad4 NFE exome AF: 0.00224

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00169 AC XY: 126 AN XY: 74466

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00228 Hom.: 2

Bravo AF: 0.00172

EpiCase AF: 0.00311

EpiControl AF: 0.00255

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	SRCAP: BP4, BP7, BS1 -
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 20, 2024	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 13, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.2
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs149628651; hg19: chr16-30715462;