X-153794596-G-C

Position:

• chrX-153794596-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001204526.1(SSR4):​c.19+11G>C variant causes a intron change. The variant allele was found at a frequency of 0.000000925 in 1,081,031 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: SSR4 NM_001204526.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.98

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-153794596-G-C is Benign according to our data. Variant chrX-153794596-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2173716.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR4	NM_001204526.1	c.19+11G>C		intron_variant			NP_001191455.1
SSR4	NM_001204527.2	c.11-78G>C		intron_variant			NP_001191456.1
SSR4	XM_047442389.1	c.68-78G>C		intron_variant			XP_047298345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSR4	ENST00000320857.7	c.-15+11G>C		intron_variant		2		ENSP00000317331	P1
SSR4	ENST00000370087.5	c.-14-78G>C		intron_variant		3		ENSP00000359104	P1
SSR4	ENST00000482902.5	n.137+11G>C		intron_variant, non_coding_transcript_variant		2
SSR4	ENST00000491833.5	n.161-78G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1081031 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 352709

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs2092127183; hg19: chrX-153060051; COSMIC: COSV54209231; COSMIC: COSV54209231;