rs2469564

Positions:

• chr15-76197614-A-G

Variant summary

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

The ENST00000388942.8(TMEM266):​c.959-4588A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,274 control chromosomes in the GnomAD database, including 1,658 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 0.14 (1658 hom., cov: 34)
• Consequence: TMEM266 ENST00000388942.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

TMEM266 (HGNC:26763): (transmembrane protein 266) Enables protein homodimerization activity. Predicted to be involved in transmembrane transport. Located in cytosol; dendrite; and plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM266 (HGNC:):

ETFA (HGNC:3481): (electron transfer flavoprotein subunit alpha) ETFA participates in catalyzing the initial step of the mitochondrial fatty acid beta-oxidation. It shuttles electrons between primary flavoprotein dehydrogenases and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. Defects in electron-transfer-flavoprotein have been implicated in type II glutaricaciduria in which multiple acyl-CoA dehydrogenase deficiencies result in large excretion of glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM266	NM_152335.5	c.935-4588A>G		intron_variant			NP_689548.3
TMEM266	XM_017021915.2	c.959-4588A>G		intron_variant			XP_016877404.1
TMEM266	XM_047432151.1	c.959-4588A>G		intron_variant			XP_047288107.1
TMEM266	XM_005254160.4	c.407-4588A>G		intron_variant			XP_005254217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM266	ENST00000388942.8	c.959-4588A>G		intron_variant		5	NM_152335.3	ENSP00000373594.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20550 AN: 152154 Hom.: 1651 Cov.: 34

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.135 AC: 20578 AN: 152274 Hom.: 1658 Cov.: 34 AF XY: 0.135 AC XY: 10055 AN XY: 74462

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.125

Alfa AF: 0.120 Hom.: 216

Bravo AF: 0.133

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.76

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: rs2469564; hg19: chr15-76489955;