rs4149549

Variant names:

• chr2-239991849-C-T
• rs4149549
• NM_004544.4:c.891-1667G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004544.4(NDUFA10):​c.891-1667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,052 control chromosomes in the GnomAD database, including 3,280 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 0.20 (3280 hom., cov: 33)
• Consequence: NDUFA10 NM_004544.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA10	NM_004544.4	c.891-1667G>A		intron_variant	Intron 8 of 9	ENST00000252711.7	NP_004535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA10	ENST00000252711.7	c.891-1667G>A		intron_variant	Intron 8 of 9	1	NM_004544.4	ENSP00000252711.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29831 AN: 151934 Hom.: 3282 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.196 AC: 29856 AN: 152052 Hom.: 3280 Cov.: 33 AF XY: 0.194 AC XY: 14389 AN XY: 74348

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.177

Alfa AF: 0.163 Hom.: 2822

Bravo AF: 0.204

Asia WGS AF: 0.210 AC: 729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.64

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: rs4149549; hg19: chr2-240931266;