3-156548853-C-T

Variant names:

• chr3-156548853-C-T
• rs6809188
• NM_007107.5:c.359+52G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007107.5(SSR3):​c.359+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,579,454 control chromosomes in the GnomAD database, including 760,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73819 hom., cov: 30)
  • Exomes 𝑓: 0.98 (686544 hom.)
• Consequence: SSR3 NM_007107.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.267
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-156548853-C-T is Benign according to our data. Variant chr3-156548853-C-T is described in ClinVar as Benign. ClinVar VariationId is 1601159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 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.359+52G>A		intron	N/A	NP_009038.1	Q9UNL2-1
	SSR3	NM_001308197.2		c.398+13G>A		intron	N/A	NP_001295126.1	Q9UNL2-2
	SSR3	NM_001308204.2		c.203+52G>A		intron	N/A	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.359+52G>A		intron	N/A	ENSP00000265044.2	Q9UNL2-1
	SSR3	ENST00000467789.5	TSL:2	c.398+13G>A		intron	N/A	ENSP00000420641.1	Q9UNL2-2
	SSR3	ENST00000896021.1		c.377+34G>A		intron	N/A	ENSP00000566080.1

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149803 AN: 152138 Hom.: 73760 Cov.: 30

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.953

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.989

GnomAD2 exomes AF: 0.984 AC: 217393 AN: 220922 AF XY: 0.984

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.991

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.962

Gnomad NFE exome AF: 0.979

Gnomad OTH exome AF: 0.982

GnomAD4 exome AF: 0.981 AC: 1399785 AN: 1427198 Hom.: 686544 Cov.: 36 AF XY: 0.981 AC XY: 695315 AN XY: 708826

African (AFR) AF: 0.997 AC: 31321 AN: 31412

American (AMR) AF: 0.990 AC: 35348 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 24329 AN: 24522

East Asian (EAS) AF: 1.00 AC: 39452 AN: 39452

South Asian (SAS) AF: 0.993 AC: 80676 AN: 81264

European-Finnish (FIN) AF: 0.964 AC: 47917 AN: 49684

Middle Eastern (MID) AF: 0.998 AC: 5588 AN: 5598

European-Non Finnish (NFE) AF: 0.979 AC: 1077259 AN: 1100642

Other (OTH) AF: 0.982 AC: 57895 AN: 58928

GnomAD4 genome AF: 0.985 AC: 149921 AN: 152256 Hom.: 73819 Cov.: 30 AF XY: 0.983 AC XY: 73165 AN XY: 74432

African (AFR) AF: 0.997 AC: 41385 AN: 41530

American (AMR) AF: 0.987 AC: 15092 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3438 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.994 AC: 4797 AN: 4828

European-Finnish (FIN) AF: 0.953 AC: 10109 AN: 10606

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66622 AN: 68028

Other (OTH) AF: 0.989 AC: 2089 AN: 2112

Alfa AF: 0.983 Hom.: 13946

Bravo AF: 0.987

Asia WGS AF: 0.996 AC: 3463 AN: 3478

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	-0.92
CADD	Benign	6.3
DANN	Benign	0.40
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6809188; hg19: chr3-156266642;