9-32553173-A-G

Variant names:

• chr9-32553173-A-G
• rs17218354
• NM_002493.5:c.*703T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002493.5. 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
	NDUFB6	NM_002493.5	MANE Select	c.*703T>C		3_prime_UTR	Exon 4 of 4	NP_002484.1
	NDUFB6	NM_182739.3		c.*703T>C		3_prime_UTR	Exon 3 of 3	NP_877416.1
	NDUFB6	NM_001199987.2		c.*703T>C		3_prime_UTR	Exon 3 of 3	NP_001186916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB6	ENST00000379847.8	TSL:1 MANE Select	c.*703T>C		3_prime_UTR	Exon 4 of 4	ENSP00000369176.3
	SMIM27	ENST00000451672.2	TSL:6	c.45+694A>G		intron	N/A	ENSP00000414891.2
	SMIM27	ENST00000425533.1	TSL:2	n.45+694A>G		intron	N/A	ENSP00000490387.1

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

African (AFR) AF: 0.296 AC: 1563 AN: 5280

American (AMR) AF: 0.354 AC: 2523 AN: 7132

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 2611 AN: 6768

East Asian (EAS) AF: 0.0777 AC: 1090 AN: 14020

South Asian (SAS) AF: 0.470 AC: 5663 AN: 12056

European-Finnish (FIN) AF: 0.377 AC: 4227 AN: 11220

Middle Eastern (MID) AF: 0.423 AC: 393 AN: 930

European-Non Finnish (NFE) AF: 0.459 AC: 55880 AN: 121726

Other (OTH) AF: 0.396 AC: 4717 AN: 11910

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

African (AFR) AF: 0.304 AC: 12603 AN: 41396

American (AMR) AF: 0.374 AC: 5715 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3470

East Asian (EAS) AF: 0.0971 AC: 502 AN: 5172

South Asian (SAS) AF: 0.475 AC: 2285 AN: 4808

European-Finnish (FIN) AF: 0.367 AC: 3857 AN: 10502

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31594 AN: 67918

Other (OTH) AF: 0.386 AC: 814 AN: 2110

Alfa AF: 0.404 Hom.: 4319

Bravo AF: 0.382

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.1
DANN	Benign	0.84
PhyloP100		0.72
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: rs17218354; hg19: chr9-32553171;