3-156544358-G-T

Variant names:

• chr3-156544358-G-T
• rs939255657
• NM_007107.5:c.441C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007107.5(SSR3):​c.441C>A​(p.Val147Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V147V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSR3 NM_007107.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 0 publications found

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]

SSR3 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=0.611 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007107.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSR3	NM_007107.5	MANE Select	c.441C>A	p.Val147Val	synonymous	Exon 4 of 5	NP_009038.1	Q9UNL2-1
	SSR3	NM_001308197.2		c.480C>A	p.Val160Val	synonymous	Exon 4 of 5	NP_001295126.1	Q9UNL2-2
	SSR3	NM_001308204.2		c.285C>A	p.Val95Val	synonymous	Exon 4 of 5	NP_001295133.1	C9J365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSR3	ENST00000265044.7	TSL:1 MANE Select	c.441C>A	p.Val147Val	synonymous	Exon 4 of 5	ENSP00000265044.2	Q9UNL2-1
	SSR3	ENST00000467789.5	TSL:2	c.480C>A	p.Val160Val	synonymous	Exon 4 of 5	ENSP00000420641.1	Q9UNL2-2
	SSR3	ENST00000896021.1		c.459C>A	p.Val153Val	synonymous	Exon 4 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443808 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717764

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32824

American (AMR) AF: 0.00 AC: 0 AN: 42970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 38848

South Asian (SAS) AF: 0.0000243 AC: 2 AN: 82342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102800

Other (OTH) AF: 0.00 AC: 0 AN: 59616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs939255657; hg19: chr3-156262147;