NM_001164496.2:c.5123G>T

Variant names:

• chr3-113296840-C-A
• rs201886712
• NM_001164496.2:c.5123G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001164496.2(CFAP44):​c.5123G>T​(p.Arg1708Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CFAP44 NM_001164496.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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]

SPICE1-CFAP44 (HGNC:58084):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2	c.5123G>T	p.Arg1708Leu	missense_variant	Exon 33 of 35	ENST00000393845.9	NP_001157968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP44	ENST00000393845.9	c.5123G>T	p.Arg1708Leu	missense_variant	Exon 33 of 35	5	NM_001164496.2	ENSP00000377428.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385040 Hom.: 0 Cov.: 35 AF XY: 0.00000146 AC XY: 1 AN XY: 683442

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.54	T
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Vest4		0.71
MutPred		0.38		Loss of MoRF binding (P = 0.0049);
MVP		0.59
MPC		0.35
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.62
gMVP		0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201886712; hg19: chr3-113015687;