14-73949943-T-G

Position:

• chr14-73949943-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152445.3(FAM161B):​c.54+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,611,776 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (72 hom.)
• Consequence: FAM161B NM_152445.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.728

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 14-73949943-T-G is Benign according to our data. Variant chr14-73949943-T-G is described in ClinVar as [Benign]. Clinvar id is 1182326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161B	NM_152445.3	c.54+30A>C		intron_variant		ENST00000286544.5	NP_689658.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161B	ENST00000286544.5	c.54+30A>C		intron_variant		1	NM_152445.3	ENSP00000286544	P1
COQ6	ENST00000554341.6	c.-150T>G		5_prime_UTR_variant, NMD_transcript_variant	1/11	1		ENSP00000450736
COQ6	ENST00000394026.8	c.-150T>G		5_prime_UTR_variant	1/12	2		ENSP00000377594
FAM161B	ENST00000651776.1	c.243+30A>C		intron_variant				ENSP00000499021

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2351 AN: 152064 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00427 AC: 1067 AN: 249748 Hom.: 28 AF XY: 0.00321 AC XY: 434 AN XY: 135140

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00181 AC: 2645 AN: 1459594 Hom.: 72 Cov.: 32 AF XY: 0.00162 AC XY: 1179 AN XY: 726050

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000280

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.0155 AC: 2360 AN: 152182 Hom.: 63 Cov.: 32 AF XY: 0.0146 AC XY: 1087 AN XY: 74414

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00251 Hom.: 4

Bravo AF: 0.0175

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.66

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: rs116578534; hg19: chr14-74416646;