NM_004544.4:c.*308C>T

Variant names:

• chr2-239960810-G-A
• rs8369
• NM_004544.4:c.*308C>T

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.*308C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,296,478 control chromosomes in the GnomAD database, including 15,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1247 hom., cov: 33)
  • Exomes 𝑓: 0.15 (14278 hom.)
• Consequence: NDUFA10 NM_004544.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.13
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-239960810-G-A is Benign according to our data. Variant chr2-239960810-G-A is described in ClinVar as Benign. ClinVar VariationId is 335198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 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.*308C>T		3_prime_UTR	Exon 10 of 10	NP_004535.1
	NDUFA10	NM_001322020.2		c.*313C>T		3_prime_UTR	Exon 9 of 9	NP_001308949.1
	NDUFA10	NR_136155.2		n.4459C>T		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.*308C>T		3_prime_UTR	Exon 10 of 10	ENSP00000252711.2
	NDUFA10	ENST00000902971.1		c.*308C>T		3_prime_UTR	Exon 11 of 11	ENSP00000573030.1
	NDUFA10	ENST00000677567.1		c.*273C>T		3_prime_UTR	Exon 11 of 11	ENSP00000503217.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17985 AN: 152134 Hom.: 1247 Cov.: 33

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.154 AC: 176623 AN: 1144228 Hom.: 14278 Cov.: 35 AF XY: 0.155 AC XY: 85019 AN XY: 549708

African (AFR) AF: 0.0377 AC: 941 AN: 24992

American (AMR) AF: 0.123 AC: 1904 AN: 15448

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 2826 AN: 14376

East Asian (EAS) AF: 0.0927 AC: 2055 AN: 22160

South Asian (SAS) AF: 0.162 AC: 9740 AN: 60200

European-Finnish (FIN) AF: 0.139 AC: 2341 AN: 16876

Middle Eastern (MID) AF: 0.145 AC: 423 AN: 2920

European-Non Finnish (NFE) AF: 0.159 AC: 149949 AN: 942650

Other (OTH) AF: 0.144 AC: 6444 AN: 44606

GnomAD4 genome AF: 0.118 AC: 17992 AN: 152250 Hom.: 1247 Cov.: 33 AF XY: 0.120 AC XY: 8960 AN XY: 74436

African (AFR) AF: 0.0441 AC: 1833 AN: 41554

American (AMR) AF: 0.123 AC: 1888 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.0874 AC: 453 AN: 5186

South Asian (SAS) AF: 0.155 AC: 747 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1602 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10262 AN: 68004

Other (OTH) AF: 0.135 AC: 286 AN: 2116

Alfa AF: 0.143 Hom.: 1268

Bravo AF: 0.113

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.95
CADD	Benign	0.091
DANN	Benign	0.55
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs8369; hg19: chr2-240900227;