10-104143598-A-T

Position:

• chr10-104143598-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025145.7(CFAP43):​c.3986T>A​(p.Val1329Asp) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP43 NM_025145.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10082707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.3986T>A	p.Val1329Asp	missense_variant	32/38	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.3986T>A	p.Val1329Asp	missense_variant	32/38	1	NM_025145.7	ENSP00000349568	P1
CFAP43	ENST00000434629.5	c.1982T>A	p.Val661Asp	missense_variant	17/23	1		ENSP00000391364
CFAP43	ENST00000457071.5	c.533T>A	p.Val178Asp	missense_variant	6/12	2		ENSP00000394274

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 20, 2023

The c.3986T>A (p.V1329D) alteration is located in exon 32 (coding exon 32) of the CFAP43 gene. This alteration results from a T to A substitution at nucleotide position 3986, causing the valine (V) at amino acid position 1329 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.63
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.079
Sift	Uncertain	0.010	D
Sift4G	Benign	0.39	T
Polyphen		0.29	B
Vest4		0.40
MutPred		0.30		Loss of sheet (P = 0.0104);
MVP		0.15
MPC		0.22
ClinPred		0.20	T
GERP RS		-5.0
Varity_R		0.21
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-105903356;