rs7088627

Positions:

• chr10-61432656-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399298.8(TMEM26):​c.271-1324A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 147,650 control chromosomes in the GnomAD database, including 34,852 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34852 hom., cov: 32)
• Consequence: TMEM26 ENST00000399298.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.75

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM26	NM_178505.8	c.271-1324A>T		intron_variant		ENST00000399298.8	NP_848600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM26	ENST00000399298.8	c.271-1324A>T		intron_variant		1	NM_178505.8	ENSP00000382237	P1
TMEM26	ENST00000488505.2	c.271-1324A>T		intron_variant, NMD_transcript_variant		1		ENSP00000426071
TMEM26	ENST00000503886.5	c.271-1324A>T		intron_variant, NMD_transcript_variant		2		ENSP00000425286

Frequencies

GnomAD3 genomes AF: 0.673 AC: 99360 AN: 147548 Hom.: 34849 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.704

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 99389 AN: 147650 Hom.: 34852 Cov.: 32 AF XY: 0.673 AC XY: 48567 AN XY: 72154

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.704

Alfa AF: 0.695 Hom.: 4622

Bravo AF: 0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.055
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs7088627; hg19: chr10-63192414;