Variant 10-61431220-G-A 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_178505.8(TMEM26):c.383C>T(p.Thr128Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000677 in 1,610,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

TMEM26
NM_178505.8 missense, splice_region

Scores

Splicing: ADA: 0.01477

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

TMEM26 (HGNC:28550): (transmembrane protein 26) This gene encodes a protein containing multiple transmembrane helices. It is a selective surface protein marker of brite/beige adipocytes, which may coexist with classical brown adipocytes in brown adipose tissue. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

TMEM26 links:

TMEM26 (HGNC:):

TMEM26 links:

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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=0.09938246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM26	NM_178505.8 linkuse as main transcript	c.383C>T	p.Thr128Met	missense_variant, splice_region_variant	3/6	ENST00000399298.8	NP_848600.2	Q6ZUK4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM26	ENST00000399298.8 linkuse as main transcript	c.383C>T	p.Thr128Met	missense_variant, splice_region_variant	3/6	1	NM_178505.8	ENSP00000382237.3	Q6ZUK4-1
TMEM26	ENST00000488505.2 linkuse as main transcript	n.383C>T		splice_region_variant, non_coding_transcript_exon_variant	3/7	1		ENSP00000426071.1	Q6ZUK4-2
TMEM26	ENST00000277749.9 linkuse as main transcript	c.113C>T	p.Thr38Met	missense_variant, splice_region_variant	1/4	5		ENSP00000277749.5	H7BXI3
TMEM26	ENST00000503886.5 linkuse as main transcript	n.383C>T		splice_region_variant, non_coding_transcript_exon_variant	3/7	2		ENSP00000425286.1	Q6ZUK4-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000764

AC:

AN:

248632

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

134876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000699

AC:

102

AN:

1458728

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.0000676

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000905

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Jun 10, 2022

The c.383C>T (p.T128M) alteration is located in exon 3 (coding exon 3) of the TMEM26 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the threonine (T) at amino acid position 128 to be replaced by a methionine (M). 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

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.23

Sift

Benign

0.11

T;D

Sift4G

Benign

0.088

T;T

Polyphen

0.94

P;.

Vest4

0.23

MVP

0.24

MPC

0.23

ClinPred

0.23

GERP RS

3.5

Varity_R

0.028

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.015

dbscSNV1_RF

Benign

0.16

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