rs863224081

Variant names:

• chr2-239961195-GA-G
• rs863224081
• NM_004544.4:c.1000-10delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004544.4(NDUFA10):​c.1000-10delT variant causes a 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 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.305
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	NM_004544.4	MANE Select	c.1000-10delT		intron	N/A	NP_004535.1	O95299-1
	NDUFA10	NM_001322020.2		c.891-10delT		intron	N/A	NP_001308949.1	A0A7I2V438
	NDUFA10	NR_136155.2		n.4083-10delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000252711.7	TSL:1 MANE Select	c.1000-10delT		intron	N/A	ENSP00000252711.2	O95299-1
	NDUFA10	ENST00000902971.1		c.1120-10delT		intron	N/A	ENSP00000573030.1
	NDUFA10	ENST00000677567.1		c.1079-10delT		intron	N/A	ENSP00000503217.1	A0A7I2V327

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

GnomAD2 exomes AF: 0.00146 AC: 365 AN: 250656 AF XY: 0.00202

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 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

African (AFR) AF: 0.000271 AC: 9 AN: 33204

American (AMR) AF: 0.000229 AC: 10 AN: 43622

Ashkenazi Jewish (ASJ) AF: 0.0000782 AC: 2 AN: 25566

East Asian (EAS) AF: 0.00 AC: 0 AN: 38450

South Asian (SAS) AF: 0.0112 AC: 961 AN: 85450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51248

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5702

European-Non Finnish (NFE) AF: 0.000115 AC: 125 AN: 1083224

Other (OTH) AF: 0.000848 AC: 50 AN: 58966

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

African (AFR) AF: 0.0000244 AC: 1 AN: 41012

American (AMR) AF: 0.00135 AC: 20 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 4914

South Asian (SAS) AF: 0.00745 AC: 35 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9764

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000196 AC: 13 AN: 66340

Other (OTH) AF: 0.00147 AC: 3 AN: 2044

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000521

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs863224081; hg19: chr2-240900612;