3-113344603-G-C

Variant names:

• chr3-113344603-G-C
• rs1262272674
• NM_001164496.2:c.3175C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164496.2(CFAP44):​c.3175C>G​(p.Arg1059Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1059Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CFAP44 NM_001164496.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08070499).

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.3175C>G	p.Arg1059Gly	missense	Exon 23 of 35	NP_001157968.1
	SPICE1-CFAP44	NR_183046.1		n.5989C>G		non_coding_transcript_exon	Exon 37 of 48
	SPICE1-CFAP44	NR_183049.1		n.6104C>G		non_coding_transcript_exon	Exon 41 of 52

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.3175C>G	p.Arg1059Gly	missense	Exon 23 of 35	ENSP00000377428.2
	CFAP44	ENST00000490481.1	TSL:5	n.297-2685C>G		intron	N/A	ENSP00000419269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1384778 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683298

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35716

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078818

Other (OTH) AF: 0.0000173 AC: 1 AN: 57908

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.16
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.024
Sift	Uncertain	0.020	D
Sift4G	Benign	0.31	T
Vest4		0.14
MutPred		0.30		Loss of helix (P = 0.0041)
MVP		0.26
MPC		0.12
ClinPred		0.49	T
GERP RS		1.9
Varity_R		0.070
gMVP		0.084
Mutation Taster		=98/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1262272674; hg19: chr3-113063450;