Variant chr13-113801690-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182614.4(TMEM255B):c.547G>A(p.Val183Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0165 in 1,611,300 control chromosomes in the GnomAD database, including 746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V183L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 56 hom., cov: 33)

Exomes 𝑓: 0.017 ( 690 hom. )

Consequence

TMEM255B
NM_182614.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.66

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025516748).

BP6

Variant 13-113801690-G-A is Benign according to our data. Variant chr13-113801690-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3179313.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM255B	NM_182614.4 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	7/9	ENST00000375353.5
TMEM255B	NM_001348663.2 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM255B	ENST00000375353.5 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	7/9	1	NM_182614.4	P1
TMEM255B	ENST00000498692.1 linkuse as main transcript	n.261G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2199

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0644

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0277

AC:

6768

AN:

244374

Hom.:

458

AF XY:

0.0223

AC XY:

2964

AN XY:

133202

show subpopulations

Gnomad AFR exome

AF:

0.00361

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000221

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.00640

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0168

AC:

24446

AN:

1458994

Hom.:

690

Cov.:

AF XY:

0.0157

AC XY:

11357

AN XY:

725684

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00390

Gnomad4 FIN exome

AF:

0.00704

Gnomad4 NFE exome

AF:

0.0152

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0145

AC:

2202

AN:

152306

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1067

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.0644

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0214

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0128

AC:

110

ExAC

AF:

0.0225

AC:

2718

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0135

EpiControl

AF:

0.0131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.21

MPC

0.37

ClinPred

0.031

GERP RS

4.7

Varity_R

0.27

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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