Variant 10-104370895-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.931G>A(p.Ala311Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CFAP58
NM_001008723.2 missense, splice_region

Scores

Splicing: ADA: 0.8405

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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:

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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=0.09064576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP58	NM_001008723.2 linkuse as main transcript	c.931G>A	p.Ala311Thr	missense_variant, splice_region_variant	7/18	ENST00000369704.8	NP_001008723.1
CFAP58	NM_001400226.1 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant, splice_region_variant	8/19		NP_001387155.1
CFAP58	NM_001400227.1 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant, splice_region_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.931G>A	p.Ala311Thr	missense_variant, splice_region_variant	7/18	1	NM_001008723.2	ENSP00000358718	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458218

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 02, 2023

The c.931G>A (p.A311T) 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 931, causing the alanine (A) at amino acid position 311 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.092

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

M_CAP

Benign

0.017

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.87

REVEL

Benign

0.023

Sift

Benign

0.36

Sift4G

Benign

0.48

Polyphen

0.032

Vest4

0.31

MutPred

0.28

Gain of phosphorylation at A311 (P = 0.1599);

MVP

0.21

MPC

0.054

ClinPred

0.43

GERP RS

3.7

Varity_R

0.082

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.84

dbscSNV1_RF

Benign

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over