Variant X-21737673-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014332.3(SMPX):c.157G>A(p.Glu53Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000662 in 1,209,198 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 3 hem. )

Consequence

SMPX
NM_014332.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

Variant links:

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 links:

SMPX (HGNC:):

SMPX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25886953).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPX	NM_014332.3 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	4/5	ENST00000379494.4	NP_055147.1	Q9UHP9A0A024RBY1
SMPX	XM_047441939.1 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	4/7		XP_047297895.1
SMPX	XM_047441940.1 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	4/5		XP_047297896.1
SMPX	NR_045617.2 linkuse as main transcript	n.344G>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMPX	ENST00000379494.4 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	4/5	1	NM_014332.3	ENSP00000368808.3	Q9UHP9
SMPX	ENST00000646008.1 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	4/5			ENSP00000493671.1	Q9UHP9
SMPX	ENST00000494525.1 linkuse as main transcript	n.157G>A		non_coding_transcript_exon_variant	4/6	5		ENSP00000495170.1	Q9UHP9

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112024

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34190

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097174

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362580

show subpopulations

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:

0.00000832

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

112024

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34190

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 18, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Arifuzzaman2018[preprint]) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

.;.;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

.;D;.

REVEL

Benign

0.25

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.21

.;T;.

Polyphen

0.0040

B;B;B

Vest4

0.65

MutPred

0.14

Gain of methylation at E53 (P = 0.0044);Gain of methylation at E53 (P = 0.0044);Gain of methylation at E53 (P = 0.0044);

MVP

0.55

MPC

0.085

ClinPred

0.96

GERP RS

6.1

Varity_R

0.77

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over