X-153796101-G-C

Position:

• chrX-153796101-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006280.3(SSR4):​c.68-333G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 208,645 control chromosomes in the GnomAD database, including 15,267 homozygotes. There are 24,575 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (7906 hom., 14711 hem., cov: 23)
  • Exomes 𝑓: 0.42 (7361 hom. 9864 hem.)
• Consequence: SSR4 NM_006280.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0370

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-153796101-G-C is Benign according to our data. Variant chrX-153796101-G-C is described in ClinVar as [Benign]. Clinvar id is 1281451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153796101-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR4	NM_006280.3	c.68-333G>C		intron_variant		ENST00000370086.8	NP_006271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSR4	ENST00000370086.8	c.68-333G>C		intron_variant		1	NM_006280.3	ENSP00000359103	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 48026 AN: 110818 Hom.: 7900 Cov.: 23 AF XY: 0.443 AC XY: 14667 AN XY: 33072

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.594

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.421 AC: 41133 AN: 97774 Hom.: 7361 Cov.: 3 AF XY: 0.468 AC XY: 9864 AN XY: 21060

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.797

Gnomad4 SAS exome AF: 0.716

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.434 AC: 48075 AN: 110871 Hom.: 7906 Cov.: 23 AF XY: 0.444 AC XY: 14711 AN XY: 33135

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.480

Alfa AF: 0.207 Hom.: 921

Bravo AF: 0.455

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.64

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: rs6643794; hg19: chrX-153061556;