chr15-81134371-C-G

Position:

• chr15-81134371-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173528.4(CFAP161):​c.42C>G​(p.Asn14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CFAP161 NM_173528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP161	NM_173528.4	c.42C>G	p.Asn14Lys	missense_variant	1/7	ENST00000286732.5	NP_775799.2
CFAP161	NM_001353365.2	c.42C>G	p.Asn14Lys	missense_variant	1/6		NP_001340294.1
CFAP161	XM_006720408.3	c.-6-899C>G		intron_variant			XP_006720471.1
CFAP161	XM_017021963.2	c.-6-899C>G		intron_variant			XP_016877452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP161	ENST00000286732.5	c.42C>G	p.Asn14Lys	missense_variant	1/7	1	NM_173528.4	ENSP00000286732.4
CFAP161	ENST00000560091.5	c.-6-899C>G		intron_variant		5		ENSP00000453414.1
CFAP161	ENST00000561216.1	c.-6-899C>G		intron_variant		4		ENSP00000454135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438614 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712912

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: 0.0000167

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 28, 2024

The c.42C>G (p.N14K) alteration is located in exon 1 (coding exon 1) of the CFAP161 gene. This alteration results from a C to G substitution at nucleotide position 42, causing the asparagine (N) at amino acid position 14 to be replaced by a lysine (K). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.58	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.72		Gain of methylation at N14 (P = 0.0037);
MVP		0.28
MPC		0.74
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.90
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1894771830; hg19: chr15-81426712;