10-104167148-T-C

Variant names:

• chr10-104167148-T-C
• rs10883974
• NM_025145.7:c.2809-430A>G

Variant summary

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

The NM_025145.7(CFAP43):​c.2809-430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,172 control chromosomes in the GnomAD database, including 4,120 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 0.22 (4120 hom., cov: 32)
• Consequence: CFAP43 NM_025145.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025145.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP43	NM_025145.7	MANE Select	c.2809-430A>G		intron	N/A	NP_079421.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP43	ENST00000357060.8	TSL:1 MANE Select	c.2809-430A>G		intron	N/A	ENSP00000349568.3
	CFAP43	ENST00000434629.5	TSL:1	c.889-430A>G		intron	N/A	ENSP00000391364.1
	ENSG00000294028	ENST00000720641.1		n.272-3038T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33794 AN: 152054 Hom.: 4113 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.222 AC: 33816 AN: 152172 Hom.: 4120 Cov.: 32 AF XY: 0.221 AC XY: 16479 AN XY: 74418

African (AFR) AF: 0.156 AC: 6459 AN: 41520

American (AMR) AF: 0.211 AC: 3228 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3468

East Asian (EAS) AF: 0.118 AC: 613 AN: 5178

South Asian (SAS) AF: 0.250 AC: 1208 AN: 4828

European-Finnish (FIN) AF: 0.235 AC: 2481 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17895 AN: 67996

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.255 Hom.: 8015

Bravo AF: 0.217

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		1.4
Mutation Taster		=99/1	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: rs10883974; hg19: chr10-105926906;