Variant 22-42087042-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002490.6(NDUFA6):c.255+18A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,536,134 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 12 hom. )

Consequence

NDUFA6
NM_002490.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870

Variant links:

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]

NDUFA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-42087042-T-G is Benign according to our data. Variant chr22-42087042-T-G is described in ClinVar as [Benign]. Clinvar id is 1600266.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00703 (1071/152280) while in subpopulation AFR AF= 0.0253 (1051/41554). AF 95% confidence interval is 0.024. There are 15 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA6	NM_002490.6 linkuse as main transcript	c.255+18A>C		intron_variant		ENST00000498737.8	NP_002481.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
NDUFA6	ENST00000498737.8 linkuse as main transcript	c.255+18A>C	intron_variant	1	NM_002490.6	ENSP00000418842	P1
NDUFA6	ENST00000617763.1 linkuse as main transcript	c.333+18A>C	intron_variant	1		ENSP00000482543
NDUFA6	ENST00000470753.1 linkuse as main transcript	c.84+18A>C	intron_variant	2		ENSP00000473478

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1067

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00189

AC:

476

AN:

251284

Hom.:

AF XY:

0.00135

AC XY:

184

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000678

AC:

938

AN:

1383854

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

401

AN XY:

693234

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000865

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00703

AC:

1071

AN:

152280

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

493

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.00787

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over