chr2-239957668-C-T

Position:

• chr2-239957668-C-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.28

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]

ACMG classification

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	UniProt
NDUFA10	NM_004544.4	c.*3450G>A		3_prime_UTR_variant	10/10	ENST00000252711.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA10	ENST00000252711.7	c.*3450G>A		3_prime_UTR_variant	10/10	1	NM_004544.4	P4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89760 AN: 151970 Hom.: 26647 Cov.: 33

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: 14 AN: 34 Hom.: 3 Cov.: 0 AF XY: 0.545 AC XY: 12 AN XY: 22

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.: 33 AF XY: 0.593 AC XY: 44073 AN XY: 74340

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

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

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. -

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

Other links and lift over

dbSNP: rs7573892; hg19: chr2-240897085;