Variant 17-78239255-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.641C>T(p.Pro214Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,541,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

TMEM235
NM_001395503.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.642

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=0.034784675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM235	NM_001395503.1 linkuse as main transcript	c.641C>T	p.Pro214Leu	missense_variant	4/5	ENST00000421688.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM235	ENST00000421688.7 linkuse as main transcript	c.641C>T	p.Pro214Leu	missense_variant	4/5	5	NM_001395503.1	P4	A6NFC5-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000470

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000261

AC:

AN:

145574

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

77954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000117

Gnomad NFE exome

AF:

0.000530

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000421

AC:

585

AN:

1389104

Hom.:

Cov.:

AF XY:

0.000427

AC XY:

293

AN XY:

685540

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000508

Gnomad4 NFE exome

AF:

0.000515

Gnomad4 OTH exome

AF:

0.000276

GnomAD4 genome

AF:

0.000276

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000707

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

Jun 30, 2022

The c.641C>T (p.P214L) 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 641, causing the proline (P) at amino acid position 214 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

Benign

0.093

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00050

T;.;.;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.63

T;T;T;.;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.035

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.52

Sift4G

Pathogenic

0.0

D;D;D;D;D

Vest4

0.094

MVP

0.28

ClinPred

0.084

GERP RS

-0.81

Varity_R

0.095

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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