7-10933663-C-T

Variant names:

• chr7-10933663-C-T
• NM_002489.4:c.219G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002489.4(COXFA4):​c.219G>A​(p.Lys73Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COXFA4 NM_002489.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-10933663-C-T is Benign according to our data. Variant chr7-10933663-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2743353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.436 with no splicing effect.

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.219G>A	p.Lys73Lys	synonymous	Exon 4 of 4	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.219G>A	p.Lys73Lys	synonymous	Exon 4 of 4	ENSP00000339720.5	O00483
	NDUFA4	ENST00000855674.1		c.219G>A	p.Lys73Lys	synonymous	Exon 5 of 5	ENSP00000525733.1
	NDUFA4	ENST00000923092.1		c.219G>A	p.Lys73Lys	synonymous	Exon 5 of 5	ENSP00000593151.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely 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	-0.42
CADD	Benign	9.4
DANN	Benign	0.57
PhyloP100		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr7-10973290;