Variant 10-61428967-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178505.8(TMEM26):c.564A>G(p.Ile188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TMEM26
NM_178505.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.516

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM26	NM_178505.8 linkuse as main transcript	c.564A>G	p.Ile188Met	missense_variant	4/6	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.564A>G	p.Ile188Met	missense_variant	4/6	1	NM_178505.8	ENSP00000382237.3	Q6ZUK4-1
TMEM26	ENST00000488505.2 linkuse as main transcript	n.564A>G		non_coding_transcript_exon_variant	4/7	1		ENSP00000426071.1	Q6ZUK4-2
TMEM26	ENST00000277749.9 linkuse as main transcript	c.294A>G	p.Ile98Met	missense_variant	2/4	5		ENSP00000277749.5	H7BXI3
TMEM26	ENST00000503886.5 linkuse as main transcript	n.564A>G		non_coding_transcript_exon_variant	4/7	2		ENSP00000425286.1	Q6ZUK4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461046

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 23, 2023

The c.564A>G (p.I188M) alteration is located in exon 4 (coding exon 4) of the TMEM26 gene. This alteration results from a A to G substitution at nucleotide position 564, causing the isoleucine (I) at amino acid position 188 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

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;T

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.7

D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.95

P;.

Vest4

0.79

MutPred

0.83

Gain of disorder (P = 0.0437);.;

MVP

0.24

MPC

0.67

ClinPred

0.98

GERP RS

-2.3

Varity_R

0.55

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over