rs3732808

Variant names:

• chr3-113401767-A-G
• rs3732808
• NM_001164496.2:c.1171-28T>C

Variant summary

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

The NM_001164496.2(CFAP44):​c.1171-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 1,576,852 control chromosomes in the GnomAD database, including 3,901 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 0.072 (446 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3455 hom.)
• Consequence: CFAP44 NM_001164496.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164496.2. 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
	CFAP44	NM_001164496.2	MANE Select	c.1171-28T>C		intron	N/A	NP_001157968.1
	CFAP44	NM_018338.3		c.1171-28T>C		intron	N/A	NP_060808.2
	SPICE1-CFAP44	NR_183045.1		n.4372-28T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.1171-28T>C		intron	N/A	ENSP00000377428.2
	CFAP44	ENST00000295868.6	TSL:1	c.1171-28T>C		intron	N/A	ENSP00000295868.2
	SPICE1-CFAP44	ENST00000649772.1		n.*1272-28T>C		intron	N/A	ENSP00000497606.1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10951 AN: 152154 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0574

GnomAD2 exomes AF: 0.0719 AC: 16048 AN: 223302 AF XY: 0.0713

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.0297

Gnomad ASJ exome AF: 0.0881

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0626

Gnomad OTH exome AF: 0.0665

GnomAD4 exome AF: 0.0642 AC: 91438 AN: 1424580 Hom.: 3455 Cov.: 29 AF XY: 0.0646 AC XY: 45682 AN XY: 706752

African (AFR) AF: 0.0937 AC: 2948 AN: 31460

American (AMR) AF: 0.0305 AC: 1142 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 2151 AN: 25076

East Asian (EAS) AF: 0.170 AC: 6529 AN: 38506

South Asian (SAS) AF: 0.0725 AC: 5830 AN: 80418

European-Finnish (FIN) AF: 0.0727 AC: 3826 AN: 52616

Middle Eastern (MID) AF: 0.0928 AC: 483 AN: 5204

European-Non Finnish (NFE) AF: 0.0591 AC: 64727 AN: 1095010

Other (OTH) AF: 0.0646 AC: 3802 AN: 58848

GnomAD4 genome AF: 0.0720 AC: 10967 AN: 152272 Hom.: 446 Cov.: 32 AF XY: 0.0721 AC XY: 5368 AN XY: 74472

African (AFR) AF: 0.0938 AC: 3896 AN: 41552

American (AMR) AF: 0.0420 AC: 643 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 311 AN: 3464

East Asian (EAS) AF: 0.152 AC: 791 AN: 5188

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4826

European-Finnish (FIN) AF: 0.0665 AC: 706 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0598 AC: 4070 AN: 68016

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0711 Hom.: 74

Bravo AF: 0.0723

Asia WGS AF: 0.104 AC: 362 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3732808; hg19: chr3-113120614; COSMIC: COSV55612771; COSMIC: COSV55612771;