chr22-42086259-AT-AT

Variant names:

• chr22-42086260-T-T
• NM_002490.6:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002490.6(NDUFA6):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFA6 NM_002490.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 0 publications found

Genes affected

NDUFA6 (HGNC:7690): (NADH:ubiquinone oxidoreductase subunit A6) This gene encodes a member of the LYR family of proteins that contain a highly conserved tripeptide (LYR) motif near the N-terminus. The encoded protein is an accessory subunit of NADH: ubiquinone oxidorerductase (Complex I), which is the largest enzyme of the mitochondrial membrane respiratory chain. Complex I functions in electron transfer from NADH to the respiratory chain. [provided by RefSeq, Oct 2016]

SMDT1 (HGNC:25055): (single-pass membrane protein with aspartate rich tail 1) This gene encodes a core regulatory component of a calcium channel in the mitochondrial inner membrane. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002490.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA6	NM_002490.6	MANE Select	c.		exon_region	Exon 3 of 3	NP_002481.3	P56556

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA6	ENST00000498737.8	TSL:1 MANE Select	c.		exon_region	Exon 3 of 3	ENSP00000418842.3	P56556
	NDUFA6	ENST00000617763.1	TSL:1	c.		exon_region	Exon 3 of 3	ENSP00000482543.1	A0A2Y9D025
	NDUFA6	ENST00000874891.1		c.		exon_region	Exon 3 of 3	ENSP00000544950.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-42482264;