X-153794541-A-G

Variant names:

• chrX-153794541-A-G
• rs112969179
• NM_001204526.2:c.-26A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204526.2(SSR4):​c.-26A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000379 in 1,054,786 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000038 (0 hom. 1 hem.)
• Consequence: SSR4 NM_001204526.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 1 publications found

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]

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

ACMG classification

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 (BayesDel_noAF=-0.35).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.0000174 AC: 2 AN: 115236 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000379 AC: 4 AN: 1054786 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 1 AN XY: 344392

African (AFR) AF: 0.00 AC: 0 AN: 25144

American (AMR) AF: 0.00 AC: 0 AN: 28108

Ashkenazi Jewish (ASJ) AF: 0.0000537 AC: 1 AN: 18623

East Asian (EAS) AF: 0.00 AC: 0 AN: 27302

South Asian (SAS) AF: 0.0000201 AC: 1 AN: 49717

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 820218

Other (OTH) AF: 0.0000225 AC: 1 AN: 44426

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		3.0
PromoterAI		-0.049	Neutral

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

Other links and lift over

dbSNP: rs112969179; hg19: chrX-153059996;