3-113382563-G-A

Variant names:

• chr3-113382563-G-A
• rs1392284
• NM_001164496.2:c.1891-1503C>T

Variant summary

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

The NM_001164496.2(CFAP44):​c.1891-1503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,838 control chromosomes in the GnomAD database, including 8,989 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 0.34 (8989 hom., cov: 32)
• Consequence: CFAP44 NM_001164496.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 4 publications found

Genes affected

CFAP44 (HGNC:25631): (cilia and flagella associated protein 44) Enables peptidase activity. Involved in sperm axoneme assembly. Acts upstream of or within microtubule cytoskeleton organization. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Implicated in spermatogenic failure 20. [provided by Alliance of Genome Resources, Apr 2022]

CFAP44 Gene-Disease associations (from GenCC):

• spermatogenic failure 20

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPICE1-CFAP44 (HGNC:58084):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2	c.1891-1503C>T		intron_variant	Intron 15 of 34	ENST00000393845.9	NP_001157968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP44	ENST00000393845.9	c.1891-1503C>T		intron_variant	Intron 15 of 34	5	NM_001164496.2	ENSP00000377428.2
SPICE1-CFAP44	ENST00000649772.1	n.*1992-649C>T		intron_variant	Intron 33 of 38			ENSP00000497606.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51015 AN: 151718 Hom.: 8985 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.336 AC: 51038 AN: 151838 Hom.: 8989 Cov.: 32 AF XY: 0.345 AC XY: 25560 AN XY: 74182

African (AFR) AF: 0.387 AC: 16029 AN: 41378

American (AMR) AF: 0.301 AC: 4588 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2934 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1730 AN: 4802

European-Finnish (FIN) AF: 0.417 AC: 4387 AN: 10522

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19117 AN: 67936

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.287 Hom.: 5287

Bravo AF: 0.328

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.38
PhyloP100		-1.3
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: rs1392284; hg19: chr3-113101410;