2-239957914-G-A

Position:

• chr2-239957914-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.223

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 -14 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_single_submitter, 1 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	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	c.*3204C>T		3_prime_UTR_variant	10/10	1	NM_004544.4	P4

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43207 AN: 152050 Hom.: 6828 Cov.: 33

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: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.284 AC: 43213 AN: 152168 Hom.: 6830 Cov.: 33 AF XY: 0.289 AC XY: 21473 AN XY: 74378

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:2

Revision: criteria provided, single submitter

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. -

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

Other links and lift over

dbSNP: rs34277046; hg19: chr2-240897331;