chr10-73291262-C-G

Variant names:

• chr10-73291262-C-G
• rs1266122956
• NM_001367801.1:c.2413G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367801.1(CFAP70):​c.2413G>C​(p.Gly805Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP70 NM_001367801.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.166
• Publications: 0 publications found

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]

CFAP70 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07589072).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367801.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP70	NM_001367801.1	MANE Select	c.2413G>C	p.Gly805Arg	missense	Exon 20 of 28	NP_001354730.1	A0A087WSW1
	CFAP70	NM_001350933.2		c.2203G>C	p.Gly735Arg	missense	Exon 19 of 27	NP_001337862.1	A0A8J8YUN0
	CFAP70	NM_001350934.2		c.1837G>C	p.Gly613Arg	missense	Exon 18 of 26	NP_001337863.1	A0A8I5KZ08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP70	ENST00000355577.9	TSL:5 MANE Select	c.2413G>C	p.Gly805Arg	missense	Exon 20 of 28	ENSP00000347781.4	A0A087WSW1
	CFAP70	ENST00000310715.8	TSL:5	c.2203G>C	p.Gly735Arg	missense	Exon 19 of 27	ENSP00000310829.4	A0A8J8YUN0
	CFAP70	ENST00000686590.1		c.1837G>C	p.Gly613Arg	missense	Exon 18 of 26	ENSP00000510588.1	A0A8I5KZ08

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.17
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.034
Sift	Benign	0.27	T
Sift4G	Benign	0.28	T
Polyphen		0.26	B
Vest4		0.17
MutPred		0.26		Gain of MoRF binding (P = 0.0179)
MVP		0.19
MPC		0.37
ClinPred		0.095	T
GERP RS		2.4
Varity_R		0.053
gMVP		0.23
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1266122956; hg19: chr10-75051020;