14-73949962-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152445.3(FAM161B):c.54+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,613,316 control chromosomes in the GnomAD database, including 6,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (471 hom., cov: 32)
  • Exomes 𝑓: 0.074 (6525 hom.)
• Consequence: FAM161B NM_152445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.266

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 14-73949962-T-C is Benign according to our data. Variant chr14-73949962-T-C is described in ClinVar as [Benign]. Clinvar id is 1227783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM161B	NM_152445.3	c.54+11A>G		intron_variant		ENST00000286544.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM161B	ENST00000286544.5	c.54+11A>G		intron_variant		1	NM_152445.3	P1
COQ6	ENST00000554341.6	c.-131T>C		5_prime_UTR_variant, NMD_transcript_variant	1/11	1
COQ6	ENST00000394026.8	c.-131T>C		5_prime_UTR_variant	1/12	2
FAM161B	ENST00000651776.1	c.243+11A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9359 AN: 152020 Hom.: 473 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0852

GnomAD3 exomes AF: 0.0950 AC: 23809 AN: 250740 Hom.: 1951 AF XY: 0.105 AC XY: 14286 AN XY: 135624

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0705

Gnomad ASJ exome AF: 0.0850

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.0760

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0948

GnomAD4 exome AF: 0.0738 AC: 107864 AN: 1461176 Hom.: 6525 Cov.: 32 AF XY: 0.0802 AC XY: 58284 AN XY: 726922

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.0712

Gnomad4 ASJ exome AF: 0.0887

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.0723

Gnomad4 NFE exome AF: 0.0557

Gnomad4 OTH exome AF: 0.0837

GnomAD4 genome AF: 0.0614 AC: 9345 AN: 152140 Hom.: 471 Cov.: 32 AF XY: 0.0661 AC XY: 4916 AN XY: 74368

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0623 Hom.: 150

Bravo AF: 0.0568

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	9.2
Dann	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs17094157; hg19: chr14-74416665; COSMIC: COSV53179715; COSMIC: COSV53179715;