rs112969179

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001204526.2(SSR4):c.-26A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,168,137 control chromosomes in the GnomAD database, including 6 homozygotes. There are 147 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., 96 hem., cov: 26)

Exomes 𝑓: 0.00024 ( 3 hom. 51 hem. )

Consequence

SSR4
NM_001204526.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.96

Publications

1 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant X-153794541-A-C is Benign according to our data. Variant chrX-153794541-A-C is described in ClinVar as Benign. ClinVar VariationId is 510069.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204526.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
SSR4	NM_001204526.2	c.-26A>C	5_prime_UTR	Exon 1 of 7	NP_001191455.1
SSR4	NM_001440795.1	c.68-133A>C	intron	N/A	NP_001427724.1
SSR4	NM_001204527.2	c.11-133A>C	intron	N/A	NP_001191456.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SSR4	ENST00000320857.7	TSL:2	c.-59A>C	5_prime_UTR	Exon 1 of 7	ENSP00000317331.3	P51571
SSR4	ENST00000939443.1		c.-147A>C	5_prime_UTR	Exon 1 of 6	ENSP00000609502.1
SSR4	ENST00000370087.5	TSL:3	c.-14-133A>C	intron	N/A	ENSP00000359104.1	P51571

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

334

AN:

113298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000551

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000686

AC:

AN:

115236

AF XY:

0.000300

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.000305

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:

0.000243

AC:

256

AN:

1054786

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

344392

show subpopulations

African (AFR)

AF:

0.00927

AC:

233

AN:

25144

American (AMR)

AF:

0.000356

AC:

AN:

28108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18623

East Asian (EAS)

AF:

0.00

AC:

AN:

27302

South Asian (SAS)

AF:

0.00

AC:

AN:

49717

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.00000366

AC:

AN:

820218

Other (OTH)

AF:

0.000225

AC:

AN:

44426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00293

AC:

332

AN:

113351

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

AN XY:

35511

show subpopulations

African (AFR)

AF:

0.0104

AC:

326

AN:

31329

American (AMR)

AF:

0.000458

AC:

AN:

10907

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6309

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53286

Other (OTH)

AF:

0.00

AC:

AN:

1556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00178

Hom.:

Bravo

AF:

0.00334

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

3.0

PromoterAI

-0.14

Neutral

(source)

Mutation Taster

=48/52

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