Variant 10-17771335-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098844.3(TMEM236):c.284T>G(p.Val95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TMEM236
NM_001098844.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

TMEM236 (HGNC:23473): (transmembrane protein 236) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM236 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11825827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM236	NM_001098844.3 linkuse as main transcript	c.284T>G	p.Val95Gly	missense_variant	2/4	ENST00000377495.2
TMEM236	XM_017016574.2 linkuse as main transcript	c.98T>G	p.Val33Gly	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM236	ENST00000377495.2 linkuse as main transcript	c.284T>G	p.Val95Gly	missense_variant	2/4	2	NM_001098844.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

234114

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126382

show subpopulations

Gnomad AFR exome

AF:

0.000378

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000443

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000669

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

Oct 24, 2023

The c.284T>G (p.V95G) alteration is located in exon 2 (coding exon 2) of the TMEM236 gene. This alteration results from a T to G substitution at nucleotide position 284, causing the valine (V) at amino acid position 95 to be replaced by a glycine (G). 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

0.25

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.11

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.43

M_CAP

Benign

0.040

MetaRNN

Benign

0.12

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

0.0040

Vest4

0.54

MVP

0.30

ClinPred

0.15

GERP RS

5.4

Varity_R

0.056

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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