rs8500

Variant names:

• chr14-73961742-G-A
• rs8500
• NM_182476.3:c.1216G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-73961742-G-A
• chr14-73961742-G-C
• chr14-73961742-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000334571.7(COQ6):​c.1216G>A​(p.Val406Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,613,496 control chromosomes in the GnomAD database, including 177,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13309 hom., cov: 31)
  • Exomes 𝑓: 0.47 (164525 hom.)
• Consequence: COQ6 ENST00000334571.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.04
• Publications: 43 publications found

Genes affected

COQ6 (HGNC:20233): (coenzyme Q6, monooxygenase) The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenzyme Q10 (or ubiquinone), which is an essential component of the mitochondrial electron transport chain, and one of the most potent lipophilic antioxidants implicated in the protection of cell damage by reactive oxygen species. Knockdown of this gene in mouse and zebrafish results in decreased growth due to increased apoptosis. Mutations in this gene are associated with autosomal recessive coenzyme Q10 deficiency-6 (COQ10D6), which manifests as nephrotic syndrome with sensorineural deafness. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2012]

ENTPD5 (HGNC:3367): (ectonucleoside triphosphate diphosphohydrolase 5 (inactive)) The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.6542964E-4).
• BP6: Variant 14-73961742-G-A is Benign according to our data. Variant chr14-73961742-G-A is described in ClinVar as Benign. ClinVar VariationId is 128834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334571.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ6	NM_182476.3	MANE Select	c.1216G>A	p.Val406Met	missense	Exon 11 of 12	NP_872282.1
	COQ6	NM_182480.3		c.1141G>A	p.Val381Met	missense	Exon 11 of 12	NP_872286.2
	COQ6	NM_001425256.1		c.1108G>A	p.Val370Met	missense	Exon 10 of 11	NP_001412185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ6	ENST00000334571.7	TSL:1 MANE Select	c.1216G>A	p.Val406Met	missense	Exon 11 of 12	ENSP00000333946.2
	COQ6	ENST00000554341.6	TSL:1	n.*821G>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000450736.2
	COQ6	ENST00000554341.6	TSL:1	n.*821G>A		3_prime_UTR	Exon 10 of 11	ENSP00000450736.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60761 AN: 151870 Hom.: 13317 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.439 AC: 110366 AN: 251462 AF XY: 0.450

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.188

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.470 AC: 686380 AN: 1461508 Hom.: 164525 Cov.: 48 AF XY: 0.472 AC XY: 343231 AN XY: 727086

African (AFR) AF: 0.207 AC: 6917 AN: 33472

American (AMR) AF: 0.405 AC: 18120 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 13008 AN: 26132

East Asian (EAS) AF: 0.238 AC: 9456 AN: 39698

South Asian (SAS) AF: 0.504 AC: 43516 AN: 86256

European-Finnish (FIN) AF: 0.538 AC: 28723 AN: 53406

Middle Eastern (MID) AF: 0.489 AC: 2823 AN: 5768

European-Non Finnish (NFE) AF: 0.482 AC: 536050 AN: 1111670

Other (OTH) AF: 0.460 AC: 27767 AN: 60384

GnomAD4 genome AF: 0.400 AC: 60765 AN: 151988 Hom.: 13309 Cov.: 31 AF XY: 0.405 AC XY: 30062 AN XY: 74294

African (AFR) AF: 0.222 AC: 9204 AN: 41462

American (AMR) AF: 0.439 AC: 6702 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5170

South Asian (SAS) AF: 0.495 AC: 2381 AN: 4812

European-Finnish (FIN) AF: 0.547 AC: 5777 AN: 10562

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32489 AN: 67930

Other (OTH) AF: 0.423 AC: 891 AN: 2108

Alfa AF: 0.452 Hom.: 80343

Bravo AF: 0.378

TwinsUK AF: 0.473 AC: 1754

ALSPAC AF: 0.479 AC: 1845

ESP6500AA AF: 0.213 AC: 940

ESP6500EA AF: 0.472 AC: 4061

ExAC AF: 0.435 AC: 52763

Asia WGS AF: 0.389 AC: 1354 AN: 3478

EpiCase AF: 0.482

EpiControl AF: 0.485

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Familial steroid-resistant nephrotic syndrome with sensorineural deafness (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.00087	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.56	N
PhyloP100		2.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.070
Sift	Benign	0.55	T
Sift4G	Benign	0.21	T
Polyphen		0.0030	B
Vest4		0.089
MPC		0.29
ClinPred		0.0059	T
GERP RS		4.1
Varity_R		0.041
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs8500; hg19: chr14-74428445; COSMIC: COSV53178775; COSMIC: COSV53178775;