rs636555

Variant names:

• chr10-104180236-C-T
• rs636555
• NM_025145.7:c.2290-304G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025145.7(CFAP43):​c.2290-304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,182 control chromosomes in the GnomAD database, including 1,155 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 0.098 (1155 hom., cov: 32)
• Consequence: CFAP43 NM_025145.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 0 publications found

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

CFAP43 Gene-Disease associations (from GenCC):

• spermatogenic failure 19

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• normal pressure hydrocephalus

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000294028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.2290-304G>A		intron_variant	Intron 17 of 37	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.2290-304G>A		intron_variant	Intron 17 of 37	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000434629.5	c.370-304G>A		intron_variant	Intron 3 of 22	1		ENSP00000391364.1
CFAP43	ENST00000278064.7	c.2293-304G>A		intron_variant	Intron 17 of 21	1		ENSP00000278064.3
ENSG00000294028	ENST00000720641.1	n.395-4578C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14804 AN: 152064 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0976 AC: 14850 AN: 152182 Hom.: 1155 Cov.: 32 AF XY: 0.0955 AC XY: 7105 AN XY: 74418

African (AFR) AF: 0.207 AC: 8599 AN: 41468

American (AMR) AF: 0.0595 AC: 909 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3468

East Asian (EAS) AF: 0.101 AC: 523 AN: 5184

South Asian (SAS) AF: 0.133 AC: 642 AN: 4826

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0510 AC: 3466 AN: 68016

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0715 Hom.: 140

Bravo AF: 0.104

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs636555; hg19: chr10-105939994;