10-73291411-C-T

Variant names:

• chr10-73291411-C-T
• rs140360144
• NM_001367801.1:c.2264G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001367801.1(CFAP70):​c.2264G>A​(p.Arg755Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,066 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (3 hom.)
• Consequence: CFAP70 NM_001367801.1 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.33
• Publications: 4 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021359742).
• BP6: Variant 10-73291411-C-T is Benign according to our data. Variant chr10-73291411-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3352589.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.2264G>A	p.Arg755Gln	missense	Exon 20 of 28	NP_001354730.1	A0A087WSW1
	CFAP70	NM_001350933.2		c.2054G>A	p.Arg685Gln	missense	Exon 19 of 27	NP_001337862.1	A0A8J8YUN0
	CFAP70	NM_001350934.2		c.1688G>A	p.Arg563Gln	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.2264G>A	p.Arg755Gln	missense	Exon 20 of 28	ENSP00000347781.4	A0A087WSW1
	CFAP70	ENST00000310715.8	TSL:5	c.2054G>A	p.Arg685Gln	missense	Exon 19 of 27	ENSP00000310829.4	A0A8J8YUN0
	CFAP70	ENST00000686590.1		c.1688G>A	p.Arg563Gln	missense	Exon 18 of 26	ENSP00000510588.1	A0A8I5KZ08

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.00191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00102 AC: 256 AN: 251424 AF XY: 0.000935

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00225 AC: 3290 AN: 1461858 Hom.: 3 Cov.: 31 AF XY: 0.00212 AC XY: 1539 AN XY: 727238

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86244

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00279 AC: 3104 AN: 1111998

Other (OTH) AF: 0.00215 AC: 130 AN: 60394

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74406

African (AFR) AF: 0.000674 AC: 28 AN: 41532

American (AMR) AF: 0.000785 AC: 12 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00167 Hom.: 0

Bravo AF: 0.00121

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00314 AC: 27

ExAC AF: 0.000906 AC: 110

EpiCase AF: 0.00213

EpiControl AF: 0.00178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CFAP70-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.11
Sift	Benign	0.52	T
Sift4G	Benign	0.53	T
Polyphen		0.89	P
Vest4		0.093
MVP		0.26
MPC		0.91
ClinPred		0.029	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.15
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs140360144; hg19: chr10-75051169; COSMIC: COSV60284105;