rs17290760

Positions:

• chr9-32556382-A-G

Variant summary

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

The NM_002493.5(NDUFB6):​c.319-2438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,318 control chromosomes in the GnomAD database, including 1,018 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 0.10 (1018 hom., cov: 33)
• Consequence: NDUFB6 NM_002493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

Genes affected

NDUFB6 (HGNC:7701): (NADH:ubiquinone oxidoreductase subunit B6) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jan 2011]

SMIM27 (HGNC:31420): (small integral membrane protein 27) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM27 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB6	NM_002493.5	c.319-2438T>C		intron_variant		ENST00000379847.8	NP_002484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB6	ENST00000379847.8	c.319-2438T>C		intron_variant		1	NM_002493.5	ENSP00000369176.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15609 AN: 152200 Hom.: 1018 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.102 AC: 15612 AN: 152318 Hom.: 1018 Cov.: 33 AF XY: 0.101 AC XY: 7487 AN XY: 74482

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0875

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.124

Alfa AF: 0.139 Hom.: 1869

Bravo AF: 0.0968

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.33

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: rs17290760; hg19: chr9-32556380;