chr2-239991849-C-T

Variant names:

• chr2-239991849-C-T
• rs4149549
• NM_004544.4:c.891-1667G>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.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
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004544.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	NM_004544.4	MANE Select	c.891-1667G>A		intron	N/A	NP_004535.1
	NDUFA10	NM_001322019.2		c.891-1667G>A		intron	N/A	NP_001308948.1
	NDUFA10	NM_001410987.1		c.891-1667G>A		intron	N/A	NP_001397916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000252711.7	TSL:1 MANE Select	c.891-1667G>A		intron	N/A	ENSP00000252711.2
	NDUFA10	ENST00000307300.8	TSL:1	c.981-1667G>A		intron	N/A	ENSP00000302321.4
	NDUFA10	ENST00000677324.1		n.1721G>A		non_coding_transcript_exon	Exon 1 of 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

African (AFR) AF: 0.298 AC: 12340 AN: 41462

American (AMR) AF: 0.190 AC: 2899 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3470

East Asian (EAS) AF: 0.187 AC: 969 AN: 5170

South Asian (SAS) AF: 0.171 AC: 825 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1361 AN: 10562

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10338 AN: 67978

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.164 Hom.: 3328

Bravo AF: 0.204

Asia WGS AF: 0.210 AC: 729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.64
PhyloP100		-1.1
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: rs4149549; hg19: chr2-240931266;