rs17218354

Positions:

• chr9-32553173-A-G
• chr9-32553173-A-T

Variant summary

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

The NM_002493.5(NDUFB6):​c.*703T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 342,892 control chromosomes in the GnomAD database, including 29,990 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 0.39 (12168 hom., cov: 31)
  • Exomes 𝑓: 0.41 (17822 hom.)
• Consequence: NDUFB6 NM_002493.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB6	NM_002493.5	c.*703T>C		3_prime_UTR_variant	4/4	ENST00000379847.8	NP_002484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB6	ENST00000379847.8	c.*703T>C		3_prime_UTR_variant	4/4	1	NM_002493.5	ENSP00000369176	P1
SMIM27	ENST00000451672.2	c.45+694A>G		intron_variant				ENSP00000414891
SMIM27	ENST00000425533.1	c.45+694A>G		intron_variant, NMD_transcript_variant		2		ENSP00000490387

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59185 AN: 151734 Hom.: 12163 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.412 AC: 78667 AN: 191042 Hom.: 17822 Cov.: 0 AF XY: 0.416 AC XY: 41649 AN XY: 100082

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.0777

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.390 AC: 59199 AN: 151850 Hom.: 12168 Cov.: 31 AF XY: 0.386 AC XY: 28659 AN XY: 74198

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.386

Alfa AF: 0.402 Hom.: 3275

Bravo AF: 0.382

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.1
DANN	Benign	0.84

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: rs17218354; hg19: chr9-32553171;