Variant X-103713633-C-A 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_182541.2(TMEM31):c.142C>A(p.Gln48Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,210,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. 8 hem. )

Consequence

TMEM31
NM_182541.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

TMEM31 (HGNC:28601): (transmembrane protein 31) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM31 links:

GLRA4 (HGNC:31715): (glycine receptor alpha 4 (pseudogene)) This gene encodes a glycine receptor and member of the ligand-gated ion channel family of proteins. The encoded protein is missing the fourth transmembrane region compared to related proteins in mouse and rat, and experimental data suggests that the human protein is functionally inactive. However, there is strong evidence to support transcription of this gene. As a result, RefSeq, in collaboration with Ensembl-GENCODE, has determined that this locus is best described as a transcribed pseudogene. [provided by RefSeq, Aug 2019]

GLRA4 links:

(HGNC:):

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=0.11224842).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM31	NM_182541.2 linkuse as main transcript	c.142C>A	p.Gln48Lys	missense_variant	3/3	ENST00000319560.7
GLRA4	NR_164162.1 linkuse as main transcript	n.1262G>T		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TMEM31	ENST00000319560.7 linkuse as main transcript	c.142C>A	p.Gln48Lys	missense_variant	3/3	1	NM_182541.2	P1
GLRA4	ENST00000674183.1 linkuse as main transcript	n.970G>T		non_coding_transcript_exon_variant	8/9
	ENST00000674243.1 linkuse as main transcript	n.1391G>T		non_coding_transcript_exon_variant	8/9
	ENST00000436213.5 linkuse as main transcript	n.1484G>T		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112393

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34539

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

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

GnomAD3 exomes

AF:

0.0000545

AC:

AN:

183516

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000732

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000337

AC:

AN:

1098266

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112393

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34539

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000943

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:

0.0000868

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.142C>A (p.Q48K) alteration is located in exon 3 (coding exon 2) of the TMEM31 gene. This alteration results from a C to A substitution at nucleotide position 142, causing the glutamine (Q) at amino acid position 48 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.45

M_CAP

Benign

0.040

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D

PROVEAN

Benign

-2.2

REVEL

Benign

0.28

Sift

Benign

0.15

Sift4G

Pathogenic

0.0

Polyphen

0.78

Vest4

0.15

MVP

0.19

MPC

0.18

ClinPred

0.22

GERP RS

5.5

Varity_R

0.48

gMVP

0.078

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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