X-21737565-A-G

Position:

• chrX-21737565-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_014332.3(SMPX):​c.265T>C​(p.Ter89Glnext*?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SMPX NM_014332.3 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64

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.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_014332.3 Downstream stopcodon found after 183 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPX	NM_014332.3	c.265T>C	p.Ter89Glnext*?	stop_lost	4/5	ENST00000379494.4	NP_055147.1
SMPX	XM_047441939.1	c.265T>C	p.Ter89Glnext*?	stop_lost	4/7		XP_047297895.1
SMPX	XM_047441940.1	c.265T>C	p.Ter89Glnext*?	stop_lost	4/5		XP_047297896.1
SMPX	NR_045617.2	n.452T>C		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPX	ENST00000379494.4	c.265T>C	p.Ter89Glnext*?	stop_lost	4/5	1	NM_014332.3	ENSP00000368808.3
SMPX	ENST00000646008.1	c.265T>C	p.Ter89Glnext*?	stop_lost	4/5			ENSP00000493671.1
SMPX	ENST00000494525.1	n.265T>C		non_coding_transcript_exon_variant	4/6	5		ENSP00000495170.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.62
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.16
GERP RS		6.2

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-21755683;