Variant 10-17796115-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001098844.3(TMEM236):c.667G>A(p.Gly223Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,678 control chromosomes in the GnomAD database, including 12,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2459 hom., cov: 31)

Exomes 𝑓: 0.11 ( 10472 hom. )

Consequence

TMEM236
NM_001098844.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.80

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004638016).

BP6

Variant 10-17796115-G-A is Benign according to our data. Variant chr10-17796115-G-A is described in ClinVar as [Benign]. Clinvar id is 982066.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM236	NM_001098844.3 linkuse as main transcript	c.667G>A	p.Gly223Arg	missense_variant	4/4	ENST00000377495.2
TMEM236	XM_017016574.2 linkuse as main transcript	c.481G>A	p.Gly161Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM236	ENST00000377495.2 linkuse as main transcript	c.667G>A	p.Gly223Arg	missense_variant	4/4	2	NM_001098844.3	P1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24177

AN:

151890

Hom.:

2456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.214

AC:

5156

AN:

24110

Hom.:

1011

AF XY:

0.207

AC XY:

2573

AN XY:

12426

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.114

AC:

166905

AN:

1461670

Hom.:

10472

Cov.:

AF XY:

0.113

AC XY:

81964

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0504

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.159

AC:

24193

AN:

152008

Hom.:

2459

Cov.:

AF XY:

0.156

AC XY:

11562

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.149

Hom.:

181

Bravo

AF:

0.175

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.17

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.55

M_CAP

Benign

0.025

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.067

Sift

Benign

0.20

Sift4G

Benign

0.19

Polyphen

0.35

Vest4

0.10

MutPred

0.39

Gain of MoRF binding (P = 0.0102);

MVP

0.12

ClinPred

0.11

GERP RS

1.4

Varity_R

0.043

gMVP

0.64

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