Variant 17-78239066-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395503.1(TMEM235):c.452C>T(p.Ser151Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000525 in 1,544,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

TMEM235
NM_001395503.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM235	NM_001395503.1 linkuse as main transcript	c.452C>T	p.Ser151Leu	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.452C>T	p.Ser151Leu	missense_variant	4/5	5	NM_001395503.1	ENSP00000402790	P4	A6NFC5-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000748

AC:

AN:

147142

Hom.:

AF XY:

0.0000382

AC XY:

AN XY:

78622

show subpopulations

Gnomad AFR exome

AF:

0.000634

Gnomad AMR exome

AF:

0.000162

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:

0.0000346

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000330

AC:

AN:

1391852

Hom.:

Cov.:

AF XY:

0.0000364

AC XY:

AN XY:

686706

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000121

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.000230

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000769

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:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000151

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

Mar 08, 2024

The c.452C>T (p.S151L) 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 452, causing the serine (S) at amino acid position 151 to be replaced by a leucine (L). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;.;.;T;.

Eigen

Benign

0.030

Eigen_PC

Benign

-0.067

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.85

D;T;T;.;.

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.43

T;T;T;T;T

MetaSVM

Uncertain

-0.045

MutationAssessor

Uncertain

2.7

M;.;.;M;.

MutationTaster

Benign

0.74

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.6

.;D;.;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

.;D;.;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Vest4

0.61

MVP

0.45

ClinPred

0.63

GERP RS

2.5

Varity_R

0.54

gMVP

0.45

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