Variant 10-104370934-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008723.2(CFAP58):c.970G>A(p.Gly324Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CFAP58
NM_001008723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

CFAP58 (HGNC:26676): (cilia and flagella associated protein 58) Involved in protein localization to motile cilium; sperm axoneme assembly; and sperm mitochondrial sheath assembly. Located in sperm midpiece. Implicated in spermatogenic failure 49. [provided by Alliance of Genome Resources, Apr 2022]

CFAP58 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11872524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP58	NM_001008723.2 linkuse as main transcript	c.970G>A	p.Gly324Arg	missense_variant	7/18	ENST00000369704.8	NP_001008723.1
CFAP58	NM_001400226.1 linkuse as main transcript	c.916G>A	p.Gly306Arg	missense_variant	8/19		NP_001387155.1
CFAP58	NM_001400227.1 linkuse as main transcript	c.916G>A	p.Gly306Arg	missense_variant	7/18		NP_001387156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP58	ENST00000369704.8 linkuse as main transcript	c.970G>A	p.Gly324Arg	missense_variant	7/18	1	NM_001008723.2	ENSP00000358718	P1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249446

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461016

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000437

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.970G>A (p.G324R) alteration is located in exon 7 (coding exon 7) of the CFAP58 gene. This alteration results from a G to A substitution at nucleotide position 970, causing the glycine (G) at amino acid position 324 to be replaced by an arginine (R). 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

0.25

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

0.026

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0067

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.90

REVEL

Benign

0.031

Sift

Benign

0.25

Sift4G

Benign

0.50

Polyphen

0.67

Vest4

0.41

MutPred

0.34

Gain of MoRF binding (P = 0.0181);

MVP

0.27

MPC

0.055

ClinPred

0.19

GERP RS

4.9

Varity_R

0.12

gMVP

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over