rs13848

Variant names:

• chr2-240007349-T-C
• rs13848
• NM_004544.4:c.771A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-240007349-T-C
• chr2-240007349-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004544.4(NDUFA10):​c.771A>G​(p.Gln257Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,582,734 control chromosomes in the GnomAD database, including 130,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11775 hom., cov: 33)
  • Exomes 𝑓: 0.40 (118448 hom.)
• Consequence: NDUFA10 NM_004544.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.205
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0091991E-4).
• BP6: Variant 2-240007349-T-C is Benign according to our data. Variant chr2-240007349-T-C is described in ClinVar as Benign. ClinVar VariationId is 129686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.205 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 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.771A>G	p.Gln257Gln	synonymous	Exon 7 of 10	NP_004535.1	O95299-1
	NDUFA10	NM_001322019.2		c.771A>G	p.Gln257Gln	synonymous	Exon 7 of 10	NP_001308948.1	H7C2X4
	NDUFA10	NM_001410987.1		c.771A>G	p.Gln257Gln	synonymous	Exon 7 of 10	NP_001397916.1	H7C1Y7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA10	ENST00000252711.7	TSL:1 MANE Select	c.771A>G	p.Gln257Gln	synonymous	Exon 7 of 10	ENSP00000252711.2	O95299-1
	NDUFA10	ENST00000307300.8	TSL:1	c.861A>G	p.Gln287Gln	synonymous	Exon 8 of 11	ENSP00000302321.4	O95299-2
	NDUFA10	ENST00000443626.5	TSL:5	c.569A>G	p.Asn190Ser	missense	Exon 5 of 7	ENSP00000411527.1	C9J6X0

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58804 AN: 151996 Hom.: 11779 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.400 AC: 99544 AN: 248804 AF XY: 0.391

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.446

Gnomad FIN exome AF: 0.517

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.401 AC: 574194 AN: 1430620 Hom.: 118448 Cov.: 30 AF XY: 0.397 AC XY: 283092 AN XY: 713180

African (AFR) AF: 0.284 AC: 9364 AN: 32978

American (AMR) AF: 0.468 AC: 20823 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 9315 AN: 25882

East Asian (EAS) AF: 0.406 AC: 16025 AN: 39504

South Asian (SAS) AF: 0.244 AC: 20929 AN: 85688

European-Finnish (FIN) AF: 0.516 AC: 27475 AN: 53224

Middle Eastern (MID) AF: 0.320 AC: 1834 AN: 5724

European-Non Finnish (NFE) AF: 0.410 AC: 444697 AN: 1083808

Other (OTH) AF: 0.400 AC: 23732 AN: 59332

GnomAD4 genome AF: 0.387 AC: 58840 AN: 152114 Hom.: 11775 Cov.: 33 AF XY: 0.391 AC XY: 29059 AN XY: 74370

African (AFR) AF: 0.295 AC: 12242 AN: 41506

American (AMR) AF: 0.449 AC: 6870 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1213 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2309 AN: 5184

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4824

European-Finnish (FIN) AF: 0.518 AC: 5476 AN: 10564

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28243 AN: 67966

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.401 Hom.: 27686

Bravo AF: 0.380

TwinsUK AF: 0.422 AC: 1563

ALSPAC AF: 0.416 AC: 1602

ESP6500AA AF: 0.292 AC: 1284

ESP6500EA AF: 0.407 AC: 3496

ExAC AF: 0.392 AC: 47595

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 1 (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 22 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	0.10
CADD	Benign	1.2
DANN	Benign	0.81
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0018	N
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-1.2	T
PhyloP100		-0.20
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.16
Sift	Uncertain	0.025	D
ClinPred		0.0044	T
GERP RS		1.7
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: rs13848; hg19: chr2-240946766; COSMIC: COSV53154298;