rs1255137785

Variant names:

• chr9-128322860-T-A
• NM_016035.5:c.2T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128322860-T-A
• chr9-128322860-T-C
• chr9-128322860-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PS1_Moderate PM2

The NM_016035.5(COQ4):​c.2T>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: COQ4 NM_016035.5 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

Genes affected

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 4 pathogenic variants. Next in-frame start position is after 25 codons. Genomic position: 128323018. Lost 0.091 part of the original CDS.
• PS1: Another start lost variant in NM_016035.5 (COQ4) was described as [Conflicting_classifications_of_pathogenicity] in ClinVar as 1033389
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5	c.2T>A	p.Met1?	start_lost	Exon 1 of 7	ENST00000300452.8	NP_057119.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ4	ENST00000300452.8	c.2T>A	p.Met1?	start_lost	Exon 1 of 7	1	NM_016035.5	ENSP00000300452.3
COQ4	ENST00000372875.3	c.2T>A	p.Met1?	start_lost	Exon 1 of 4	2		ENSP00000361966.3
COQ4	ENST00000608951.5	c.2T>A	p.Met1?	start_lost	Exon 1 of 3	2		ENSP00000476323.1
COQ4	ENST00000609948.1	c.2T>A	p.Met1?	start_lost	Exon 1 of 2	2		ENSP00000477292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410984 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 698952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0059	T;T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.63	N;.;.;N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;.;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.45	P;.;.;P
Vest4		0.78
MutPred		0.98		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.34
ClinPred		1.0	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.96
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131085139;