Genetic Variant NM_007107.5:c.482A>G (chr3-156544317-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007107.5(SSR3):c.482A>G(p.Asn161Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,589,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SSR3
NM_007107.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.91

Publications

1 publications found

Variant links:

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

SSR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2772383).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSR3	NM_007107.5	MANE Select	c.482A>G	p.Asn161Ser	missense	Exon 4 of 5	NP_009038.1	Q9UNL2-1
SSR3	NM_001308197.2		c.521A>G	p.Asn174Ser	missense	Exon 4 of 5	NP_001295126.1	Q9UNL2-2
SSR3	NM_001308204.2		c.326A>G	p.Asn109Ser	missense	Exon 4 of 5	NP_001295133.1	C9J365

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSR3	ENST00000265044.7	TSL:1 MANE Select	c.482A>G	p.Asn161Ser	missense	Exon 4 of 5	ENSP00000265044.2	Q9UNL2-1
SSR3	ENST00000467789.5	TSL:2	c.521A>G	p.Asn174Ser	missense	Exon 4 of 5	ENSP00000420641.1	Q9UNL2-2
SSR3	ENST00000896021.1		c.500A>G	p.Asn167Ser	missense	Exon 4 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000422

AC:

AN:

236744

AF XY:

0.0000469

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.0000581

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000181

AC:

AN:

1437306

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

714058

show subpopulations

African (AFR)

AF:

0.000185

AC:

AN:

32416

American (AMR)

AF:

0.00

AC:

AN:

41524

Ashkenazi Jewish (ASJ)

AF:

0.0000784

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

38810

South Asian (SAS)

AF:

0.0000373

AC:

AN:

80438

European-Finnish (FIN)

AF:

0.0000378

AC:

AN:

52864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1100756

Other (OTH)

AF:

0.0000169

AC:

AN:

59310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.093

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

PhyloP100

7.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.29

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.72

MVP

0.25

MPC

0.31

ClinPred

0.11

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.65

Mutation Taster

=69/31

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over