14-73950052-C-CAGTGACAGCGAT

Position:

• chr14-73950052-C-CAGTGACAGCGAT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000286544.5(FAM161B):​c.-27_-26insATCGCTGTCACT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,610,690 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (4 hom.)
• Consequence: FAM161B ENST00000286544.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.03

Genes affected

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-73950052-C-CAGTGACAGCGAT is Benign according to our data. Variant chr14-73950052-C-CAGTGACAGCGAT is described in ClinVar as [Likely_benign]. Clinvar id is 517856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161B	NM_152445.3	c.-27_-26insATCGCTGTCACT		5_prime_UTR_variant	1/9	ENST00000286544.5	NP_689658.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161B	ENST00000286544.5	c.-27_-26insATCGCTGTCACT		5_prime_UTR_variant	1/9	1	NM_152445.3	ENSP00000286544	P1
COQ6	ENST00000554341.6	c.-36_-25dup		5_prime_UTR_variant, NMD_transcript_variant	1/11	1		ENSP00000450736
FAM161B	ENST00000651776.1	c.163_164insATCGCTGTCACT	p.Tyr51_His54dup	inframe_insertion	1/9			ENSP00000499021
COQ6	ENST00000394026.8	c.-36_-25dup		5_prime_UTR_variant	1/12	2		ENSP00000377594

Frequencies

GnomAD3 genomes AF: 0.000637 AC: 97 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000964 AC: 238 AN: 246804 Hom.: 1 AF XY: 0.00105 AC XY: 141 AN XY: 134076

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0000532

Gnomad NFE exome AF: 0.000337

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.000589 AC: 859 AN: 1458366 Hom.: 4 Cov.: 32 AF XY: 0.000632 AC XY: 459 AN XY: 725700

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000637 AC: 97 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74492

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00199 Hom.: 1

EpiCase AF: 0.000600

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 21, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs547039179; hg19: chr14-74416755;