15-81136552-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173528.4(CFAP161):c.196T>A(p.Tyr66Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP161 NM_173528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30

Genes affected

CFAP161 (HGNC:26782): (cilia and flagella associated protein 161)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP161	NM_173528.4	c.196T>A	p.Tyr66Asn	missense_variant	3/7	ENST00000286732.5
CFAP161	NM_001353365.2	c.196T>A	p.Tyr66Asn	missense_variant	3/6
CFAP161	XM_006720408.3	c.121T>A	p.Tyr41Asn	missense_variant	4/8
CFAP161	XM_017021963.2	c.121T>A	p.Tyr41Asn	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP161	ENST00000286732.5	c.196T>A	p.Tyr66Asn	missense_variant	3/7	1	NM_173528.4	P1
CFAP161	ENST00000560091.5	c.121T>A	p.Tyr41Asn	missense_variant	4/5	5
CFAP161	ENST00000561216.1	c.121T>A	p.Tyr41Asn	missense_variant	4/4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249564 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135398

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.196T>A (p.Y66N) alteration is located in exon 3 (coding exon 3) of the CFAP161 gene. This alteration results from a T to A substitution at nucleotide position 196, causing the tyrosine (Y) at amino acid position 66 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	20
Dann	Uncertain	0.98
Eigen	Benign	0.068
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.59	T
MutationTaster	Benign	0.56	N
PROVEAN	Pathogenic	-6.4	D;D;D
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.99	.;.;D
Vest4		0.54
MutPred		0.66		.;.;Loss of sheet (P = 0.0457);
MVP		0.082
MPC		0.30
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.39
gMVP		0.76

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: rs1567157821; hg19: chr15-81428893;