rs13424612

Variant names:

• chr2-239960704-C-T
• rs13424612
• NM_004544.4:c.*414G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-239960704-C-T
• chr2-239960704-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004544.4(NDUFA10):​c.*414G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,159,702 control chromosomes in the GnomAD database, including 63,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6954 hom., cov: 34)
  • Exomes 𝑓: 0.33 (56687 hom.)
• Consequence: NDUFA10 NM_004544.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.03
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-239960704-C-T is Benign according to our data. Variant chr2-239960704-C-T is described in ClinVar as Benign. ClinVar VariationId is 335193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	NM_004544.4	MANE Select	c.*414G>A		3_prime_UTR	Exon 10 of 10	NP_004535.1	O95299-1
	NDUFA10	NM_001322020.2		c.*419G>A		3_prime_UTR	Exon 9 of 9	NP_001308949.1	A0A7I2V438
	NDUFA10	NR_136155.2		n.4565G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000252711.7	TSL:1 MANE Select	c.*414G>A		3_prime_UTR	Exon 10 of 10	ENSP00000252711.2	O95299-1
	NDUFA10	ENST00000678455.1		c.*414G>A		3_prime_UTR	Exon 10 of 10	ENSP00000504395.1	A0A7I2V594
	NDUFA10	ENST00000678914.1		c.*414G>A		3_prime_UTR	Exon 10 of 10	ENSP00000504515.1	A0A7I2YQU0

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43269 AN: 152074 Hom.: 6952 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.331 AC: 333556 AN: 1007510 Hom.: 56687 Cov.: 33 AF XY: 0.328 AC XY: 156879 AN XY: 478388

African (AFR) AF: 0.122 AC: 2560 AN: 21018

American (AMR) AF: 0.303 AC: 3172 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 2651 AN: 9358

East Asian (EAS) AF: 0.377 AC: 4500 AN: 11948

South Asian (SAS) AF: 0.185 AC: 9154 AN: 49598

European-Finnish (FIN) AF: 0.438 AC: 3461 AN: 7904

Middle Eastern (MID) AF: 0.213 AC: 479 AN: 2254

European-Non Finnish (NFE) AF: 0.345 AC: 296089 AN: 858952

Other (OTH) AF: 0.319 AC: 11490 AN: 36002

GnomAD4 genome AF: 0.284 AC: 43274 AN: 152192 Hom.: 6954 Cov.: 34 AF XY: 0.288 AC XY: 21425 AN XY: 74404

African (AFR) AF: 0.138 AC: 5713 AN: 41542

American (AMR) AF: 0.306 AC: 4677 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5178

South Asian (SAS) AF: 0.190 AC: 915 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4800 AN: 10578

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.342 AC: 23282 AN: 67996

Other (OTH) AF: 0.272 AC: 576 AN: 2116

Alfa AF: 0.313 Hom.: 20372

Bravo AF: 0.269

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.60
PhyloP100		-2.0
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: rs13424612; hg19: chr2-240900121;