Variant 2-239957668-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004544.4(NDUFA10):c.*3450G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,122 control chromosomes in the GnomAD database, including 26,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26669 hom., cov: 33)

Exomes 𝑓: 0.41 ( 3 hom. )

Consequence

NDUFA10
NM_004544.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

NDUFA10 (HGNC:7684): (NADH:ubiquinone oxidoreductase subunit A10) The protein encoded by this gene is a component of 42 kDa complex I, the first enzyme complex in the electron transport chain of mitochondria. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. A mutation in this gene was found in an individual with Leigh syndrome. [provided by RefSeq, Apr 2016]

NDUFA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 2-239957668-C-T is Benign according to our data. Variant chr2-239957668-C-T is described in ClinVar as [Benign]. Clinvar id is 335152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA10	NM_004544.4 linkuse as main transcript	c.*3450G>A		3_prime_UTR_variant	10/10	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7 linkuse as main transcript	c.*3450G>A		3_prime_UTR_variant	10/10	1	NM_004544.4	ENSP00000252711	P4	O95299-1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89760

AN:

151970

Hom.:

26647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.412

AC:

AN:

Hom.:

Cov.:

AF XY:

0.545

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.591

AC:

89835

AN:

152088

Hom.:

26669

Cov.:

AF XY:

0.593

AC XY:

44073

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.666

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.570

Alfa

AF:

0.582

Hom.:

8892

Bravo

AF:

0.592

Asia WGS

AF:

0.572

AC:

1989

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.15

DANN

Benign

0.48

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