Variant 10-104364753-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001008723.2(CFAP58):c.461T>C(p.Phe154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,610,878 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 4 hom., cov: 31)

Exomes 𝑓: 0.010 ( 103 hom. )

Consequence

CFAP58
NM_001008723.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.754

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006124586).

BP6

Variant 10-104364753-T-C is Benign according to our data. Variant chr10-104364753-T-C is described in ClinVar as [Benign]. Clinvar id is 3387901.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0104 (15122/1460994) while in subpopulation NFE AF= 0.0126 (13954/1111506). AF 95% confidence interval is 0.0124. There are 103 homozygotes in gnomad4_exome. There are 7336 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP58	NM_001008723.2 linkuse as main transcript	c.461T>C	p.Phe154Ser	missense_variant	4/18	ENST00000369704.8	NP_001008723.1	Q5T655
CFAP58	NM_001400226.1 linkuse as main transcript	c.407T>C	p.Phe136Ser	missense_variant	5/19		NP_001387155.1
CFAP58	NM_001400227.1 linkuse as main transcript	c.407T>C	p.Phe136Ser	missense_variant	4/18		NP_001387156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP58	ENST00000369704.8 linkuse as main transcript	c.461T>C	p.Phe154Ser	missense_variant	4/18	1	NM_001008723.2	ENSP00000358718.3		Q5T655

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

1018

AN:

149766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00816

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00429

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.00685

GnomAD3 exomes

AF:

0.00674

AC:

1687

AN:

250454

Hom.:

AF XY:

0.00633

AC XY:

857

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.00536

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00802

GnomAD4 exome

AF:

0.0104

AC:

15122

AN:

1460994

Hom.:

103

Cov.:

AF XY:

0.0101

AC XY:

7336

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00520

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000592

Gnomad4 FIN exome

AF:

0.00543

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.00863

GnomAD4 genome

AF:

0.00679

AC:

1018

AN:

149884

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

454

AN XY:

73016

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00814

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00429

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.00678

Alfa

AF:

0.00927

Hom.:

Bravo

AF:

0.00678

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.00683

AC:

829

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.0120

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

CFAP58: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.027

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.27

REVEL

Benign

0.045

Sift

Benign

0.40

Sift4G

Benign

0.40

Polyphen

0.023

Vest4

0.46

MVP

0.099

MPC

0.064

ClinPred

0.0085

GERP RS

3.2

Varity_R

0.050

gMVP

0.25

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