15-81136622-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173528.4(CFAP161):c.266A>T(p.Asp89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFAP161 NM_173528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33615476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP161	NM_173528.4	c.266A>T	p.Asp89Val	missense_variant	3/7	ENST00000286732.5
CFAP161	NM_001353365.2	c.266A>T	p.Asp89Val	missense_variant	3/6
CFAP161	XM_006720408.3	c.191A>T	p.Asp64Val	missense_variant	4/8
CFAP161	XM_017021963.2	c.191A>T	p.Asp64Val	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP161	ENST00000286732.5	c.266A>T	p.Asp89Val	missense_variant	3/7	1	NM_173528.4	P1
CFAP161	ENST00000560091.5	c.191A>T	p.Asp64Val	missense_variant	4/5	5
CFAP161	ENST00000561216.1	c.191A>T	p.Asp64Val	missense_variant	4/4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Dec 21, 2023

The c.266A>T (p.D89V) alteration is located in exon 3 (coding exon 3) of the CFAP161 gene. This alteration results from a A to T substitution at nucleotide position 266, causing the aspartic acid (D) at amino acid position 89 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-2.5	D;D;D
Sift	Benign	0.035	D;T;D
Sift4G	Uncertain	0.021	D;T;T
Polyphen		0.93	.;.;P
Vest4		0.57
MutPred		0.52		.;.;Gain of sheet (P = 0.0221);
MVP		0.29
MPC		0.31
ClinPred		0.94	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-81428963;