Variant chr17-78234601-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395503.1(TMEM235):c.280C>T(p.Arg94Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,536,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

TMEM235
NM_001395503.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.162

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13540706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM235	NM_001395503.1 linkuse as main transcript	c.280C>T	p.Arg94Cys	missense_variant	3/5	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.280C>T	p.Arg94Cys	missense_variant	3/5	5	NM_001395503.1	ENSP00000402790	P4	A6NFC5-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000340

AC:

AN:

135342

Hom.:

AF XY:

0.000380

AC XY:

AN XY:

73612

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.000327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000476

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000583

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000755

AC:

1045

AN:

1383856

Hom.:

Cov.:

AF XY:

0.000722

AC XY:

493

AN XY:

682872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000929

Gnomad4 OTH exome

AF:

0.000501

GnomAD4 genome

AF:

0.000236

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000137

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

Aug 17, 2021

The c.280C>T (p.R94C) alteration is located in exon 4 (coding exon 3) of the TMEM235 gene. This alteration results from a C to T substitution at nucleotide position 280, causing the arginine (R) at amino acid position 94 to be replaced by a cysteine (C). 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

0.28

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.73

T;T;.;.

M_CAP

Benign

0.083

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.4

M;.;M;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-4.0

.;D;D;D

REVEL

Benign

0.28

Sift

Benign

0.035

.;D;T;D

Sift4G

Uncertain

0.032

D;D;D;D

Vest4

0.22

MutPred

0.57

.;Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);

MVP

0.63

ClinPred

0.30

GERP RS

1.4

Varity_R

0.18

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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