Genetic Variant SSR3:p.Arg110Lys (chr3-156548935-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007107.5(SSR3):c.329G>A(p.Arg110Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,508 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SSR3
NM_007107.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009923577).

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.329G>A	p.Arg110Lys	missense	Exon 3 of 5	NP_009038.1	Q9UNL2-1
SSR3	NM_001308197.2		c.329G>A	p.Arg110Lys	missense	Exon 3 of 5	NP_001295126.1	Q9UNL2-2
SSR3	NM_001308204.2		c.173G>A	p.Arg58Lys	missense	Exon 3 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.329G>A	p.Arg110Lys	missense	Exon 3 of 5	ENSP00000265044.2	Q9UNL2-1
SSR3	ENST00000467789.5	TSL:2	c.329G>A	p.Arg110Lys	missense	Exon 3 of 5	ENSP00000420641.1	Q9UNL2-2
SSR3	ENST00000896021.1		c.329G>A	p.Arg110Lys	missense	Exon 3 of 5	ENSP00000566080.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000223

AC:

AN:

251032

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

170

AN:

1461250

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00162

AC:

140

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53076

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111838

Other (OTH)

AF:

0.000132

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.0000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00125

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000677

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.14

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-3.0

PhyloP100

4.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

1.4

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.20

MutPred

0.38

Gain of glycosylation at S105 (P = 0.0037)

MVP

0.34

MPC

0.30

ClinPred

0.067

GERP RS

5.4

Varity_R

0.25

gMVP

0.54

Mutation Taster

=49/51

disease causing

(source)

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

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