3-156544421-A-G

Position:

• chr3-156544421-A-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_007107.5(SSR3):​c.378T>C​(p.Asn126Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,584,122 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (17 hom.)
• Consequence: SSR3 NM_007107.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.227

Genes affected

SSR3 (HGNC:11325): (signal sequence receptor subunit 3) The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR is comprised of four membrane proteins/subunits: alpha, beta, gamma, and delta. The first two are glycosylated subunits and the latter two are non-glycosylated subunits. This gene encodes the gamma subunit, which is predicted to span the membrane four times. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-156544421-A-G is Benign according to our data. Variant chr3-156544421-A-G is described in ClinVar as [Benign]. Clinvar id is 788520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.227 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00723 (1102/152358) while in subpopulation AFR AF= 0.0251 (1042/41588). AF 95% confidence interval is 0.0238. There are 12 homozygotes in gnomad4. There are 533 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR3	NM_007107.5	c.378T>C	p.Asn126Asn	synonymous_variant	4/5	ENST00000265044.7	NP_009038.1
SSR3	NM_001308197.2	c.417T>C	p.Asn139Asn	synonymous_variant	4/5		NP_001295126.1
SSR3	NM_001308204.2	c.222T>C	p.Asn74Asn	synonymous_variant	4/5		NP_001295133.1
SSR3	NM_001308205.2	c.222T>C	p.Asn74Asn	synonymous_variant	4/5		NP_001295134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSR3	ENST00000265044.7	c.378T>C	p.Asn126Asn	synonymous_variant	4/5	1	NM_007107.5	ENSP00000265044.2

Frequencies

GnomAD3 genomes AF: 0.00721 AC: 1097 AN: 152240 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00207 AC: 474 AN: 229054 Hom.: 9 AF XY: 0.00142 AC XY: 176 AN XY: 123808

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00143

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000395

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.000842 AC: 1206 AN: 1431764 Hom.: 17 Cov.: 30 AF XY: 0.000765 AC XY: 544 AN XY: 710716

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.000794

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000792

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00723 AC: 1102 AN: 152358 Hom.: 12 Cov.: 32 AF XY: 0.00715 AC XY: 533 AN XY: 74510

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00218 Hom.: 2

Bravo AF: 0.00833

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 16, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.7
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.8

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: rs6768440; hg19: chr3-156262210;