22-42086498-C-G

Position:

• chr22-42086498-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002490.6(NDUFA6):​c.256-184G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,080 control chromosomes in the GnomAD database, including 11,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.38 (11341 hom., cov: 32)
• Consequence: NDUFA6 NM_002490.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-42086498-C-G is Benign according to our data. Variant chr22-42086498-C-G is described in ClinVar as [Benign]. Clinvar id is 1287028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA6	NM_002490.6	c.256-184G>C		intron_variant		ENST00000498737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA6	ENST00000498737.8	c.256-184G>C		intron_variant		1	NM_002490.6	P1
NDUFA6	ENST00000617763.1	c.334-184G>C		intron_variant		1
NDUFA6	ENST00000470753.1	c.85-184G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57162 AN: 151958 Hom.: 11305 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.376 AC: 57248 AN: 152080 Hom.: 11341 Cov.: 32 AF XY: 0.378 AC XY: 28074 AN XY: 74324

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.375

Alfa AF: 0.366 Hom.: 1439

Bravo AF: 0.374

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.73

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: rs4147641; hg19: chr22-42482502;