rs1915440

Positions:

• chr10-61436376-A-C
• chr10-61436376-A-G

Variant summary

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

The NM_178505.8(TMEM26):​c.192-128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 525,628 control chromosomes in the GnomAD database, including 46,091 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 0.47 (18153 hom., cov: 31)
  • Exomes 𝑓: 0.37 (27938 hom.)
• Consequence: TMEM26 NM_178505.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM26	NM_178505.8	c.192-128T>G		intron_variant		ENST00000399298.8	NP_848600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM26	ENST00000399298.8	c.192-128T>G		intron_variant		1	NM_178505.8	ENSP00000382237	P1
TMEM26	ENST00000488505.2	c.192-128T>G		intron_variant, NMD_transcript_variant		1		ENSP00000426071
TMEM26	ENST00000503886.5	c.192-128T>G		intron_variant, NMD_transcript_variant		2		ENSP00000425286

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70613 AN: 151750 Hom.: 18118 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.375 AC: 140155 AN: 373762 Hom.: 27938 AF XY: 0.372 AC XY: 73808 AN XY: 198238

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.466 AC: 70706 AN: 151866 Hom.: 18153 Cov.: 31 AF XY: 0.468 AC XY: 34746 AN XY: 74216

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.466

Alfa AF: 0.344 Hom.: 4171

Bravo AF: 0.472

Asia WGS AF: 0.406 AC: 1408 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.28

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: rs1915440; hg19: chr10-63196134;