Variant 13-113801811-T-C 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_182614.4(TMEM255B):c.668T>C(p.Met223Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000108 in 1,602,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TMEM255B
NM_182614.4 missense, splice_region

Scores

Splicing: ADA: 0.03833

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19517043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM255B	NM_182614.4 linkuse as main transcript	c.668T>C	p.Met223Thr	missense_variant, splice_region_variant	7/9	ENST00000375353.5
TMEM255B	NM_001348663.2 linkuse as main transcript	c.668T>C	p.Met223Thr	missense_variant, splice_region_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM255B	ENST00000375353.5 linkuse as main transcript	c.668T>C	p.Met223Thr	missense_variant, splice_region_variant	7/9	1	NM_182614.4	P1
TMEM255B	ENST00000498692.1 linkuse as main transcript	n.382T>C		splice_region_variant, non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000126

AC:

AN:

230230

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

124914

show subpopulations

Gnomad AFR exome

AF:

0.0000697

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:

0.00

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1449888

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

720232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000198

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

May 28, 2024

The c.668T>C (p.M223T) alteration is located in exon 7 (coding exon 7) of the TMEM255B gene. This alteration results from a T to C substitution at nucleotide position 668, causing the methionine (M) at amino acid position 223 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.16

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

M_CAP

Benign

0.024

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0020

Polyphen

0.80

Vest4

0.31

MVP

0.32

MPC

0.088

ClinPred

0.15

GERP RS

3.5

Varity_R

0.59

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.038

dbscSNV1_RF

Benign

0.17

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