10-61436376-A-C

Variant names:

• chr10-61436376-A-C
• rs1915440
• NM_178505.8:c.192-128T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178505.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM26	NM_178505.8	MANE Select	c.192-128T>G		intron	N/A	NP_848600.2
	TMEM26	NR_134507.2		n.492-128T>G		intron	N/A
	TMEM26	NR_134508.2		n.492-128T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM26	ENST00000399298.8	TSL:1 MANE Select	c.192-128T>G		intron	N/A	ENSP00000382237.3
	TMEM26	ENST00000488505.2	TSL:1	n.192-128T>G		intron	N/A	ENSP00000426071.1
	TMEM26	ENST00000503886.5	TSL:2	n.192-128T>G		intron	N/A	ENSP00000425286.1

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

African (AFR) AF: 0.693 AC: 7017 AN: 10126

American (AMR) AF: 0.426 AC: 5589 AN: 13106

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 3808 AN: 11984

East Asian (EAS) AF: 0.376 AC: 10408 AN: 27690

South Asian (SAS) AF: 0.339 AC: 9640 AN: 28396

European-Finnish (FIN) AF: 0.480 AC: 12472 AN: 25992

Middle Eastern (MID) AF: 0.470 AC: 788 AN: 1678

European-Non Finnish (NFE) AF: 0.351 AC: 81797 AN: 232922

Other (OTH) AF: 0.395 AC: 8636 AN: 21868

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

African (AFR) AF: 0.691 AC: 28597 AN: 41408

American (AMR) AF: 0.447 AC: 6825 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1109 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2045 AN: 5154

South Asian (SAS) AF: 0.345 AC: 1655 AN: 4804

European-Finnish (FIN) AF: 0.492 AC: 5170 AN: 10506

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23813 AN: 67938

Other (OTH) AF: 0.466 AC: 985 AN: 2112

Alfa AF: 0.346 Hom.: 4674

Bravo AF: 0.472

Asia WGS AF: 0.406 AC: 1408 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.28
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1915440; hg19: chr10-63196134;