2-240011011-C-T

Variant names:

• chr2-240011011-C-T
• rs6437237
• NM_004544.4:c.749+606G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004544.4(NDUFA10):​c.749+606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,898 control chromosomes in the GnomAD database, including 19,426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19426 hom., cov: 32)
• Consequence: NDUFA10 NM_004544.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 22

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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 rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4	c.749+606G>A		intron_variant	Intron 6 of 9	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7	c.749+606G>A		intron_variant	Intron 6 of 9	1	NM_004544.4	ENSP00000252711.2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76588 AN: 151778 Hom.: 19420 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.505 AC: 76634 AN: 151898 Hom.: 19426 Cov.: 32 AF XY: 0.506 AC XY: 37594 AN XY: 74226

African (AFR) AF: 0.492 AC: 20377 AN: 41388

American (AMR) AF: 0.508 AC: 7754 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1603 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3435 AN: 5160

South Asian (SAS) AF: 0.411 AC: 1980 AN: 4816

European-Finnish (FIN) AF: 0.583 AC: 6144 AN: 10540

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33760 AN: 67938

Other (OTH) AF: 0.466 AC: 987 AN: 2116

Alfa AF: 0.500 Hom.: 2416

Bravo AF: 0.499

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6437237; hg19: chr2-240950428;