chr3-156548985-C-T

Variant names:

• chr3-156548985-C-T
• rs9296
• NM_007107.5:c.279G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_007107.5(SSR3):​c.279G>A​(p.Glu93Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,612,430 control chromosomes in the GnomAD database, including 15,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1554 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13573 hom.)
• Consequence: SSR3 NM_007107.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.885
• Publications: 8 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 3-156548985-C-T is Benign according to our data. Variant chr3-156548985-C-T is described in ClinVar as Benign. ClinVar VariationId is 1537157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.885 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

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.279G>A	p.Glu93Glu	synonymous	Exon 3 of 5	NP_009038.1	Q9UNL2-1
	SSR3	NM_001308197.2		c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 5	NP_001295126.1	Q9UNL2-2
	SSR3	NM_001308204.2		c.123G>A	p.Glu41Glu	synonymous	Exon 3 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.279G>A	p.Glu93Glu	synonymous	Exon 3 of 5	ENSP00000265044.2	Q9UNL2-1
	SSR3	ENST00000467789.5	TSL:2	c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 5	ENSP00000420641.1	Q9UNL2-2
	SSR3	ENST00000896021.1		c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21269 AN: 151996 Hom.: 1540 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.146 AC: 36555 AN: 250206 AF XY: 0.147

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.0901

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.133 AC: 194146 AN: 1460314 Hom.: 13573 Cov.: 36 AF XY: 0.134 AC XY: 97253 AN XY: 726516

African (AFR) AF: 0.149 AC: 4966 AN: 33434

American (AMR) AF: 0.161 AC: 7183 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 2295 AN: 26110

East Asian (EAS) AF: 0.200 AC: 7917 AN: 39648

South Asian (SAS) AF: 0.175 AC: 15051 AN: 86186

European-Finnish (FIN) AF: 0.142 AC: 7468 AN: 52572

Middle Eastern (MID) AF: 0.114 AC: 654 AN: 5762

European-Non Finnish (NFE) AF: 0.126 AC: 140502 AN: 1111580

Other (OTH) AF: 0.134 AC: 8110 AN: 60350

GnomAD4 genome AF: 0.140 AC: 21315 AN: 152116 Hom.: 1554 Cov.: 33 AF XY: 0.141 AC XY: 10494 AN XY: 74354

African (AFR) AF: 0.142 AC: 5884 AN: 41486

American (AMR) AF: 0.153 AC: 2340 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1108 AN: 5184

South Asian (SAS) AF: 0.177 AC: 851 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1502 AN: 10562

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8878 AN: 68000

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.130 Hom.: 863

Bravo AF: 0.138

Asia WGS AF: 0.239 AC: 828 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	9.6
DANN	Benign	0.53
PhyloP100		0.89
Mutation Taster		=93/7	polymorphism (auto)

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: rs9296; hg19: chr3-156266774; COSMIC: COSV54020635;