NM_002493.5:c.*703T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002493.5(NDUFB6):​c.*703T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000522 in 191,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: NDUFB6 NM_002493.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

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>G		3_prime_UTR	Exon 4 of 4	NP_002484.1
	NDUFB6	NM_182739.3		c.*703T>G		3_prime_UTR	Exon 3 of 3	NP_877416.1
	NDUFB6	NM_001199987.2		c.*703T>G		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>G		3_prime_UTR	Exon 4 of 4	ENSP00000369176.3
	SMIM27	ENST00000451672.2	TSL:6	c.45+694A>C		intron	N/A	ENSP00000414891.2
	SMIM27	ENST00000425533.1	TSL:2	n.45+694A>C		intron	N/A	ENSP00000490387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000522 AC: 1 AN: 191654 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 100420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5296

American (AMR) AF: 0.00 AC: 0 AN: 7168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6802

East Asian (EAS) AF: 0.00 AC: 0 AN: 14030

South Asian (SAS) AF: 0.00 AC: 0 AN: 12110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 932

European-Non Finnish (NFE) AF: 0.00000819 AC: 1 AN: 122116

Other (OTH) AF: 0.00 AC: 0 AN: 11944

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		0.72

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;