rs17552038

Variant names:

• chr14-73950242-G-C
• rs17552038
• ENST00000554341.6:n.88+62G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-73950242-G-C
• chr14-73950242-G-T

Variant summary

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

The ENST00000553462.6(COQ6):​n.24G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,538,458 control chromosomes in the GnomAD database, including 17,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1279 hom., cov: 33)
  • Exomes 𝑓: 0.15 (15825 hom.)
• Consequence: COQ6 ENST00000553462.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.15
• Publications: 9 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]

FAM161B (HGNC:19854): (FAM161 centrosomal protein B) Predicted to be involved in cilium organization. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-73950242-G-C is Benign according to our data. Variant chr14-73950242-G-C is described in ClinVar as Benign. ClinVar VariationId is 1291437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553462.6. 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_182480.3		c.88+62G>C		intron	N/A	NP_872286.2
	COQ6	NM_001425258.1		c.88+62G>C		intron	N/A	NP_001412187.1
	COQ6	NM_001425259.1		c.-4+62G>C		intron	N/A	NP_001412188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ6	ENST00000554341.6	TSL:1	n.88+62G>C		intron	N/A	ENSP00000450736.2
	COQ6	ENST00000553462.6	TSL:5	n.24G>C		non_coding_transcript_exon	Exon 1 of 5
	FAM161B	ENST00000651776.1		c.-27C>G		5_prime_UTR	Exon 1 of 9	ENSP00000499021.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17305 AN: 152238 Hom.: 1278 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.156 AC: 22237 AN: 142360 AF XY: 0.151

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0685

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.145 AC: 201255 AN: 1386100 Hom.: 15825 Cov.: 33 AF XY: 0.144 AC XY: 98387 AN XY: 684284

African (AFR) AF: 0.0229 AC: 724 AN: 31612

American (AMR) AF: 0.281 AC: 10067 AN: 35762

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3292 AN: 25190

East Asian (EAS) AF: 0.0790 AC: 2826 AN: 35754

South Asian (SAS) AF: 0.115 AC: 9150 AN: 79650

European-Finnish (FIN) AF: 0.152 AC: 5352 AN: 35114

Middle Eastern (MID) AF: 0.0817 AC: 465 AN: 5694

European-Non Finnish (NFE) AF: 0.150 AC: 161485 AN: 1079366

Other (OTH) AF: 0.136 AC: 7894 AN: 57958

GnomAD4 genome AF: 0.114 AC: 17307 AN: 152358 Hom.: 1279 Cov.: 33 AF XY: 0.114 AC XY: 8459 AN XY: 74516

African (AFR) AF: 0.0285 AC: 1184 AN: 41600

American (AMR) AF: 0.192 AC: 2936 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.0778 AC: 404 AN: 5192

South Asian (SAS) AF: 0.116 AC: 560 AN: 4834

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9853 AN: 68030

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.136 Hom.: 312

Bravo AF: 0.119

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-2.2
PromoterAI		-0.18	Neutral
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: rs17552038; hg19: chr14-74416945; COSMIC: COSV53178557; COSMIC: COSV53178557;