rs12769490

Positions:

• chr10-104355789-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008723.2(CFAP58):​c.9+1883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,244 control chromosomes in the GnomAD database, including 3,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3828 hom., cov: 33)
• Consequence: CFAP58 NM_001008723.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP58	NM_001008723.2	c.9+1883T>C		intron_variant		ENST00000369704.8	NP_001008723.1
CFAP58	NM_001400226.1	c.-45-2552T>C		intron_variant			NP_001387155.1
CFAP58	NM_001400227.1	c.-45-2552T>C		intron_variant			NP_001387156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP58	ENST00000369704.8	c.9+1883T>C		intron_variant		1	NM_001008723.2	ENSP00000358718	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31736 AN: 152124 Hom.: 3830 Cov.: 33

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0769

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31730 AN: 152244 Hom.: 3828 Cov.: 33 AF XY: 0.207 AC XY: 15379 AN XY: 74438

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0771

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.232

Alfa AF: 0.259 Hom.: 2492

Bravo AF: 0.200

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs12769490; hg19: chr10-106115547;