rs398122848

Positions:

• chrX-21743751-TC-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_014332.3(SMPX):​c.130delG​(p.Glu44fs) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SMPX NM_014332.3 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.17

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-21743751-TC-T is Pathogenic according to our data. Variant chrX-21743751-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 29948.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-21743751-TC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPX	NM_014332.3	c.130delG	p.Glu44fs	frameshift_variant, splice_region_variant	3/5	ENST00000379494.4	NP_055147.1
SMPX	XM_047441939.1	c.130delG	p.Glu44fs	frameshift_variant, splice_region_variant	3/7		XP_047297895.1
SMPX	XM_047441940.1	c.130delG	p.Glu44fs	frameshift_variant, splice_region_variant	3/5		XP_047297896.1
SMPX	NR_045617.2	n.317delG		splice_region_variant, non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPX	ENST00000379494.4	c.130delG	p.Glu44fs	frameshift_variant, splice_region_variant	3/5	1	NM_014332.3	ENSP00000368808.3
SMPX	ENST00000646008.1	c.130delG	p.Glu44fs	frameshift_variant, splice_region_variant	3/5			ENSP00000493671.1
SMPX	ENST00000494525.1	n.130delG		splice_region_variant, non_coding_transcript_exon_variant	3/6	5		ENSP00000495170.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

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

May 13, 2011

- -

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: rs398122848; hg19: chrX-21761869;