Variant 10-17771381-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001098844.3(TMEM236):c.330G>C(p.Glu110Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00214 in 1,613,498 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E110K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

TMEM236
NM_001098844.3 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.45

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 10-17771381-G-C is Benign according to our data. Variant chr10-17771381-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2672394.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-17771381-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM236	NM_001098844.3 linkuse as main transcript	c.330G>C	p.Glu110Asp	missense_variant, splice_region_variant	2/4	ENST00000377495.2
TMEM236	XM_017016574.2 linkuse as main transcript	c.144G>C	p.Glu48Asp	missense_variant, splice_region_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM236	ENST00000377495.2 linkuse as main transcript	c.330G>C	p.Glu110Asp	missense_variant, splice_region_variant	2/4	2	NM_001098844.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00114

AC:

279

AN:

245138

Hom.:

AF XY:

0.00116

AC XY:

154

AN XY:

132412

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.000240

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00224

AC:

3280

AN:

1461266

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1593

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152232

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00121

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00250

AC:

ExAC

AF:

0.00111

AC:

132

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

TMEM236: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

M_CAP

Benign

0.021

MetaRNN

Benign

0.032

MetaSVM

Uncertain

0.18

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.26

Sift

Benign

0.056

Sift4G

Uncertain

0.048

Polyphen

0.99

Vest4

0.38

MutPred

0.19

Loss of ubiquitination at K113 (P = 0.0787);

MVP

0.20

ClinPred

0.034

GERP RS

5.5

Varity_R

0.14

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: 0

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