Variant X-120291267-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001104544.3(TMEM255A):c.338T>C(p.Phe113Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,095,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

TMEM255A
NM_001104544.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87

Variant links:

Genes affected

TMEM255A (HGNC:26086): (transmembrane protein 255A) Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM255A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM255A	NM_001104544.3 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant	4/9	ENST00000371369.9	NP_001098014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM255A	ENST00000371369.9 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant	4/9	2	NM_001104544.3	ENSP00000360420	P1	Q5JRV8-3
TMEM255A	ENST00000309720.9 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant	4/10	1		ENSP00000310110		Q5JRV8-1
TMEM255A	ENST00000440464.5 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant	4/7	5		ENSP00000405781		Q5JRV8-4
TMEM255A	ENST00000519908.1 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant	4/6	5		ENSP00000428013

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1095505

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361125

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000131

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 18, 2023

The c.338T>C (p.F113S) alteration is located in exon 4 (coding exon 4) of the TMEM255A gene. This alteration results from a T to C substitution at nucleotide position 338, causing the phenylalanine (F) at amino acid position 113 to be replaced by a serine (S). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;.;.

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

D;D;T;D

M_CAP

Pathogenic

0.38

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.2

M;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-7.5

D;D;D;D

REVEL

Pathogenic

0.65

Sift

Benign

0.044

D;D;D;T

Sift4G

Pathogenic

0.0010

D;D;D;.

Polyphen

1.0

D;.;.;.

Vest4

0.93

MutPred

0.65

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.87

MPC

0.65

ClinPred

1.0

GERP RS

5.3

Varity_R

0.90

gMVP

0.98

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