X-21737572-A-AGCTT

Position:

• chrX-21737572-A-AGCTT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_014332.3(SMPX):​c.254_257dupAAGC​(p.Glu87fs) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SMPX NM_014332.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0375 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPX	NM_014332.3	c.254_257dupAAGC	p.Glu87fs	frameshift_variant	4/5	ENST00000379494.4	NP_055147.1
SMPX	XM_047441939.1	c.254_257dupAAGC	p.Glu87fs	frameshift_variant	4/7		XP_047297895.1
SMPX	XM_047441940.1	c.254_257dupAAGC	p.Glu87fs	frameshift_variant	4/5		XP_047297896.1
SMPX	NR_045617.2	n.441_444dupAAGC		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPX	ENST00000379494.4	c.254_257dupAAGC	p.Glu87fs	frameshift_variant	4/5	1	NM_014332.3	ENSP00000368808.3
SMPX	ENST00000646008.1	c.254_257dupAAGC	p.Glu87fs	frameshift_variant	4/5			ENSP00000493671.1
SMPX	ENST00000494525.1	n.254_257dupAAGC		non_coding_transcript_exon_variant	4/6	5		ENSP00000495170.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 14, 2023

This sequence change creates a premature translational stop signal (p.Glu87Serfs*2) in the SMPX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the SMPX protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMPX-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-21755690;