X-153794719-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006280.3(SSR4):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,211,090 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SSR4
NM_006280.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.58

Publications

0 publications found

Variant links:

Genes affected

SSR4 (HGNC:11326): (signal sequence receptor subunit 4) This gene encodes the delta subunit of the translocon-associated protein complex which is involved in translocating proteins across the endoplasmic reticulum membrane. The encoded protein is located in the Xq28 region and is arranged in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene and both genes are driven by a CpG-embedded bidirectional promoter. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

SSR4 links:

IDH3G (HGNC:5386): (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma) Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the gamma subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. This gene is a candidate gene for periventricular heterotopia. Several alternatively spliced transcript variants of this gene have been described, but only some of their full length natures have been determined. [provided by RefSeq, Jul 2008]

IDH3G Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

IDH3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10841116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006280.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSR4	NM_006280.3	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 6	NP_006271.1	P51571
SSR4	NM_001440795.1		c.113C>T	p.Ala38Val	missense	Exon 2 of 7	NP_001427724.1
SSR4	NM_001204526.2		c.65C>T	p.Ala22Val	missense	Exon 2 of 7	NP_001191455.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSR4	ENST00000370086.8	TSL:1 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 6	ENSP00000359103.3	P51571
SSR4	ENST00000320857.7	TSL:2	c.32C>T	p.Ala11Val	missense	Exon 2 of 7	ENSP00000317331.3	P51571
SSR4	ENST00000370087.5	TSL:3	c.32C>T	p.Ala11Val	missense	Exon 2 of 7	ENSP00000359104.1	P51571

Frequencies

GnomAD3 genomes

AF:

0.0000176

AC:

AN:

113549

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000639

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000554

AC:

AN:

180505

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000780

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097488

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26393

American (AMR)

AF:

0.00

AC:

AN:

35188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.00

AC:

AN:

30191

South Asian (SAS)

AF:

0.00

AC:

AN:

54097

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841919

Other (OTH)

AF:

0.00

AC:

AN:

46018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000176

AC:

AN:

113602

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

35738

show subpopulations

African (AFR)

AF:

0.0000637

AC:

AN:

31382

American (AMR)

AF:

0.00

AC:

AN:

10895

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3607

South Asian (SAS)

AF:

0.00

AC:

AN:

2830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6351

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53406

Other (OTH)

AF:

0.00

AC:

AN:

1562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.74

M_CAP

Benign

0.047

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

1.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.26

REVEL

Benign

0.076

Sift

Benign

0.13

Sift4G

Benign

0.14

Polyphen

0.10

Vest4

0.29

MVP

0.42

MPC

0.63

ClinPred

0.10

GERP RS

4.2

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.30

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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