7-10938647-A-G

Variant names:

• chr7-10938647-A-G
• rs10272132
• NM_002489.4:c.131+161T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002489.4(COXFA4):​c.131+161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 590,868 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (452 hom., cov: 33)
  • Exomes 𝑓: 0.022 (324 hom.)
• Consequence: COXFA4 NM_002489.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.426
• Publications: 0 publications found

Genes affected

COXFA4 (HGNC:7687): (NDUFA4 mitochondrial complex associated) The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

COXFA4 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-10938647-A-G is Benign according to our data. Variant chr7-10938647-A-G is described in ClinVar as Benign. ClinVar VariationId is 682709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002489.4. 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
	COXFA4	NM_002489.4	MANE Select	c.131+161T>C		intron	N/A	NP_002480.1	O00483

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA4	ENST00000339600.6	TSL:1 MANE Select	c.131+161T>C		intron	N/A	ENSP00000339720.5	O00483
	NDUFA4	ENST00000855674.1		c.131+161T>C		intron	N/A	ENSP00000525733.1
	NDUFA4	ENST00000923092.1		c.131+161T>C		intron	N/A	ENSP00000593151.1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7853 AN: 152140 Hom.: 452 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.0223 AC: 9789 AN: 438610 Hom.: 324 Cov.: 5 AF XY: 0.0202 AC XY: 4735 AN XY: 233972

African (AFR) AF: 0.140 AC: 1711 AN: 12222

American (AMR) AF: 0.0668 AC: 1288 AN: 19272

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 160 AN: 13612

East Asian (EAS) AF: 0.0830 AC: 2350 AN: 28310

South Asian (SAS) AF: 0.00450 AC: 199 AN: 44256

European-Finnish (FIN) AF: 0.0227 AC: 743 AN: 32670

Middle Eastern (MID) AF: 0.0194 AC: 36 AN: 1854

European-Non Finnish (NFE) AF: 0.0103 AC: 2705 AN: 262240

Other (OTH) AF: 0.0247 AC: 597 AN: 24174

GnomAD4 genome AF: 0.0516 AC: 7864 AN: 152258 Hom.: 452 Cov.: 33 AF XY: 0.0509 AC XY: 3787 AN XY: 74448

African (AFR) AF: 0.135 AC: 5603 AN: 41536

American (AMR) AF: 0.0459 AC: 703 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.0713 AC: 370 AN: 5190

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4828

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 740 AN: 68010

Other (OTH) AF: 0.0492 AC: 104 AN: 2114

Alfa AF: 0.0234 Hom.: 24

Bravo AF: 0.0587

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.51
PhyloP100		0.43
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: rs10272132; hg19: chr7-10978274;