Variant chr2-239957914-G-A 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.*3204C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,176 control chromosomes in the GnomAD database, including 6,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6830 hom., cov: 33)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

NDUFA10
NM_004544.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.223

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-239957914-G-A is Benign according to our data. Variant chr2-239957914-G-A is described in ClinVar as [Benign]. Clinvar id is 335156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA10	NM_004544.4 linkuse as main transcript	c.*3204C>T		3_prime_UTR_variant	10/10	ENST00000252711.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA10	ENST00000252711.7 linkuse as main transcript	c.*3204C>T		3_prime_UTR_variant	10/10	1	NM_004544.4	P4	O95299-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43207

AN:

152050

Hom.:

6828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.167

GnomAD4 genome

AF:

0.284

AC:

43213

AN:

152168

Hom.:

6830

Cov.:

AF XY:

0.289

AC XY:

21473

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.376

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.306

Hom.:

1859

Bravo

AF:

0.269

Asia WGS

AF:

0.261

AC:

909

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

-0.91

CADD

Benign

0.86

DANN

Benign

0.51

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