rs398122930

Positions:

• chrX-21743782-TG-T
• chrX-21743782-TG-TGG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_014332.3(SMPX):​c.99delC​(p.Arg34fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SMPX NM_014332.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.703

Genes affected

SMPX (HGNC:11122): (small muscle protein X-linked) This gene encodes a small protein that has no known functional domains. Mutations in this gene are a cause of X-linked deafness-4, and the encoded protein may play a role in the maintenance of inner ear cells subjected to mechanical stress. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2011]

SMPX (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.629 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-21743782-TG-T is Pathogenic according to our data. Variant chrX-21743782-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 40063.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-21743782-TG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPX	NM_014332.3	c.99delC	p.Arg34fs	frameshift_variant	3/5	ENST00000379494.4	NP_055147.1
SMPX	XM_047441939.1	c.99delC	p.Arg34fs	frameshift_variant	3/7		XP_047297895.1
SMPX	XM_047441940.1	c.99delC	p.Arg34fs	frameshift_variant	3/5		XP_047297896.1
SMPX	NR_045617.2	n.286delC		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPX	ENST00000379494.4	c.99delC	p.Arg34fs	frameshift_variant	3/5	1	NM_014332.3	ENSP00000368808.3
SMPX	ENST00000646008.1	c.99delC	p.Arg34fs	frameshift_variant	3/5			ENSP00000493671.1
SMPX	ENST00000494525.1	n.99delC		non_coding_transcript_exon_variant	3/6	5		ENSP00000495170.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096493 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362007

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hearing loss, X-linked 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

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: rs398122930; hg19: chrX-21761900;