14-73950079-T-G

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.-53A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,606,566 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (139 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (155 hom.)
• Consequence: FAM161B NM_152445.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.55

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 (MetaRNN=0.0016567409).
• BP6: Variant 14-73950079-T-G is Benign according to our data. Variant chr14-73950079-T-G is described in ClinVar as [Benign]. Clinvar id is 136984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM161B	NM_152445.3	c.-53A>C		5_prime_UTR_variant	1/9	ENST00000286544.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM161B	ENST00000286544.5	c.-53A>C		5_prime_UTR_variant	1/9	1	NM_152445.3	P1
COQ6	ENST00000554341.6	c.-14T>G		5_prime_UTR_variant, NMD_transcript_variant	1/11	1
FAM161B	ENST00000651776.1	c.137A>C	p.His46Pro	missense_variant	1/9
COQ6	ENST00000394026.8	c.-14T>G		5_prime_UTR_variant	1/12	2

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3670 AN: 152112 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00650 AC: 1570 AN: 241524 Hom.: 75 AF XY: 0.00499 AC XY: 659 AN XY: 131938

Gnomad AFR exome AF: 0.0921

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000341

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.00255 AC: 3715 AN: 1454338 Hom.: 155 Cov.: 32 AF XY: 0.00219 AC XY: 1588 AN XY: 723854

Gnomad4 AFR exome AF: 0.0904

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.00491

GnomAD4 genome AF: 0.0242 AC: 3677 AN: 152228 Hom.: 139 Cov.: 32 AF XY: 0.0223 AC XY: 1661 AN XY: 74452

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.00850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00157 Hom.: 2

Bravo AF: 0.0280

ExAC AF: 0.00754 AC: 914

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2013

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

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.065
Dann	Benign	0.38
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.022
Sift	Benign	0.065	T
Vest4		0.13
MVP		0.030
MPC		0.098
ClinPred		0.036	T
GERP RS		-11

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: rs190881382; hg19: chr14-74416782;