chr10-73291330-G-C

Variant names:

• chr10-73291330-G-C
• rs2048166254
• NM_001367801.1:c.2345C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367801.1(CFAP70):​c.2345C>G​(p.Thr782Ser) 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: CFAP70 NM_001367801.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151

Genes affected

CFAP70 (HGNC:30726): (cilia and flagella associated protein 70) Predicted to be involved in cilium assembly and cilium movement. Located in ciliary basal body and sperm flagellum. Part of outer dynein arm. Implicated in spermatogenic failure 41. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037174106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP70	NM_001367801.1	c.2345C>G	p.Thr782Ser	missense_variant	Exon 20 of 28	ENST00000355577.9	NP_001354730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP70	ENST00000355577.9	c.2345C>G	p.Thr782Ser	missense_variant	Exon 20 of 28	5	NM_001367801.1	ENSP00000347781.4

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

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2345C>G (p.T782S) alteration is located in exon 20 (coding exon 19) of the CFAP70 gene. This alteration results from a C to G substitution at nucleotide position 2345, causing the threonine (T) at amino acid position 782 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.14
DANN	Benign	0.26
DEOGEN2	Benign	0.0049	T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.13	T;T;.
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.76	N;N;.
REVEL	Benign	0.014
Sift	Benign	0.58	T;T;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0060	B;.;.
Vest4		0.11
MutPred		0.22		Gain of glycosylation at T782 (P = 0.0158);.;.;
MVP		0.088
MPC		0.27
ClinPred		0.022	T
GERP RS		-5.0
Varity_R		0.041
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2048166254; hg19: chr10-75051088;