10-73275535-A-C

Variant names:

• chr10-73275535-A-C
• NM_001367801.1:c.2794T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001367801.1(CFAP70):​c.2794T>G​(p.Tyr932Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 4.73

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]

DNAJC9-AS1 (HGNC:31432): (DNAJC9 and MRPS16 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP70	NM_001367801.1	c.2794T>G	p.Tyr932Asp	missense_variant	Exon 23 of 28	ENST00000355577.9	NP_001354730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP70	ENST00000355577.9	c.2794T>G	p.Tyr932Asp	missense_variant	Exon 23 of 28	5	NM_001367801.1	ENSP00000347781.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2794T>G (p.Y932D) alteration is located in exon 23 (coding exon 22) of the CFAP70 gene. This alteration results from a T to G substitution at nucleotide position 2794, causing the tyrosine (Y) at amino acid position 932 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	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.65	T;T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.48	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.7	D;D;.;.
REVEL	Uncertain	0.51
Sift	Benign	0.047	D;D;.;.
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.95	P;.;.;.
Vest4		0.88
MutPred		0.71		Gain of phosphorylation at Y931 (P = 0.0988);.;.;.;
MVP		0.51
MPC		0.95
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.66
gMVP		0.72

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: chr10-75035293;