rs9296

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-156548985-C-G
• chr3-156548985-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007107.5(SSR3):​c.279G>C​(p.Glu93Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E93E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSR3 NM_007107.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Glu93Asp	missense	Exon 3 of 5	NP_009038.1	Q9UNL2-1
	SSR3	NM_001308197.2		c.279G>C	p.Glu93Asp	missense	Exon 3 of 5	NP_001295126.1	Q9UNL2-2
	SSR3	NM_001308204.2		c.123G>C	p.Glu41Asp	missense	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>C	p.Glu93Asp	missense	Exon 3 of 5	ENSP00000265044.2	Q9UNL2-1
	SSR3	ENST00000467789.5	TSL:2	c.279G>C	p.Glu93Asp	missense	Exon 3 of 5	ENSP00000420641.1	Q9UNL2-2
	SSR3	ENST00000896021.1		c.279G>C	p.Glu93Asp	missense	Exon 3 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.89
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.28	T
Sift4G	Benign	0.47	T
Polyphen		0.061	B
Vest4		0.65
MutPred		0.52		Gain of glycosylation at S97 (P = 0.0146)
MVP		0.75
MPC		0.31
ClinPred		0.61	D
GERP RS		3.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.17
gMVP		0.74
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;