3-156548982-ATCCT-A

Variant names:

• chr3-156548982-ATCCT-A
• rs1719856599
• NM_007107.5:c.278_281delAGGA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_007107.5(SSR3):​c.278_281delAGGA​(p.Glu93ValfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E93E) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSR3 NM_007107.5 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.84
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-156548982-ATCCT-A is Pathogenic according to our data. Variant chr3-156548982-ATCCT-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 982233.Status of the report is no_assertion_criteria_provided, 0 stars.

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.278_281delAGGA	p.Glu93ValfsTer7	frameshift	Exon 3 of 5	NP_009038.1	Q9UNL2-1
	SSR3	NM_001308197.2		c.278_281delAGGA	p.Glu93ValfsTer7	frameshift	Exon 3 of 5	NP_001295126.1	Q9UNL2-2
	SSR3	NM_001308204.2		c.122_125delAGGA	p.Glu41ValfsTer7	frameshift	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.278_281delAGGA	p.Glu93ValfsTer7	frameshift	Exon 3 of 5	ENSP00000265044.2	Q9UNL2-1
	SSR3	ENST00000467789.5	TSL:2	c.278_281delAGGA	p.Glu93ValfsTer7	frameshift	Exon 3 of 5	ENSP00000420641.1	Q9UNL2-2
	SSR3	ENST00000896021.1		c.278_281delAGGA	p.Glu93ValfsTer7	frameshift	Exon 3 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1719856599; hg19: chr3-156266771;