Variant 17-78239081-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395503.1(TMEM235):c.467C>T(p.Ala156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,544,366 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

TMEM235
NM_001395503.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

TMEM235 (HGNC:27563): (transmembrane protein 235) Predicted to be located in cytoplasm. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM235 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021889806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM235	NM_001395503.1 linkuse as main transcript	c.467C>T	p.Ala156Val	missense_variant	4/5	ENST00000421688.7	NP_001382432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM235	ENST00000421688.7 linkuse as main transcript	c.467C>T	p.Ala156Val	missense_variant	4/5	5	NM_001395503.1	ENSP00000402790.2		A6NFC5-1

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000346

AC:

AN:

147500

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

78784

show subpopulations

Gnomad AFR exome

AF:

0.000506

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000979

Gnomad NFE exome

AF:

0.000754

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.00105

AC:

1459

AN:

1392016

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

665

AN XY:

686830

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.000261

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000558

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000852

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000836

Hom.:

Bravo

AF:

0.000589

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000263

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 13, 2021

The c.467C>T (p.A156V) alteration is located in exon 5 (coding exon 4) of the TMEM235 gene. This alteration results from a C to T substitution at nucleotide position 467, causing the alanine (A) at amino acid position 156 to be replaced by a valine (V). 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

0.091

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.086

DANN

Benign

0.85

DEOGEN2

Benign

0.0054

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.48

T;T;T;.;.

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.022

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

N;.;.;N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

.;N;.;N;N

REVEL

Benign

0.038

Sift

Benign

0.28

.;T;.;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Vest4

0.037

MVP

0.067

ClinPred

0.0053

GERP RS

-4.1

Varity_R

0.032

gMVP

0.16

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