Variant chr13-113766232-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182614.4(TMEM255B):c.164T>C(p.Val55Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000388 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

TMEM255B
NM_182614.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

Variant links:

Genes affected

TMEM255B (HGNC:28297): (transmembrane protein 255B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM255B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3394013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM255B	NM_182614.4 linkuse as main transcript	c.164T>C	p.Val55Ala	missense_variant	2/9	ENST00000375353.5
TMEM255B	NM_001348663.2 linkuse as main transcript	c.164T>C	p.Val55Ala	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TMEM255B	ENST00000375353.5 linkuse as main transcript	c.164T>C	p.Val55Ala	missense_variant	2/9	1	NM_182614.4	P1
TMEM255B	ENST00000488362.5 linkuse as main transcript	c.164T>C	p.Val55Ala	missense_variant	2/5	2
TMEM255B	ENST00000483678.5 linkuse as main transcript	n.69T>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

251344

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000409

AC:

598

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000395

AC XY:

287

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000190

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

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

Oct 12, 2022

The c.164T>C (p.V55A) alteration is located in exon 2 (coding exon 2) of the TMEM255B gene. This alteration results from a T to C substitution at nucleotide position 164, causing the valine (V) at amino acid position 55 to be replaced by an alanine (A). 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

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

2.9

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.2

.;D

REVEL

Benign

0.24

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.97

.;D

Vest4

0.61

MVP

0.34

MPC

0.35

ClinPred

0.35

GERP RS

3.2

Varity_R

0.26

gMVP

0.70

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