rs863224081

Positions:

• chr2-239961195-GA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004544.4(NDUFA10):​c.1000-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,573,550 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00082 (17 hom.)
• Consequence: NDUFA10 NM_004544.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.305

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 -16 ACMG points.

• BP6: Variant 2-239961195-GA-G is Benign according to our data. Variant chr2-239961195-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 214700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000493 (73/148118) while in subpopulation SAS AF= 0.00745 (35/4700). AF 95% confidence interval is 0.0055. There are 1 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA10	NM_004544.4	c.1000-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000252711.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA10	ENST00000252711.7	c.1000-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004544.4	P4

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 73 AN: 148004 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00744

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000196

Gnomad OTH AF: 0.00148

GnomAD3 exomes AF: 0.00146 AC: 365 AN: 250656 Hom.: 4 AF XY: 0.00202 AC XY: 274 AN XY: 135556

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000822 AC: 1171 AN: 1425432 Hom.: 17 Cov.: 34 AF XY: 0.00119 AC XY: 847 AN XY: 709548

Gnomad4 AFR exome AF: 0.000271

Gnomad4 AMR exome AF: 0.000229

Gnomad4 ASJ exome AF: 0.0000782

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0112

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.000848

GnomAD4 genome AF: 0.000493 AC: 73 AN: 148118 Hom.: 1 Cov.: 33 AF XY: 0.000652 AC XY: 47 AN XY: 72082

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000196

Gnomad4 OTH AF: 0.00147

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 30, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 12, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Benign, flagged submission

clinical testing

GeneDx

Apr 02, 2014

The variant is found in MITONUC-MITOP panel(s). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs863224081; hg19: chr2-240900612;