NM_001164496.2:c.4860G>A

Variant names:

• chr3-113305051-C-T
• rs62001862
• NM_001164496.2:c.4860G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001164496.2(CFAP44):​c.4860G>A​(p.Pro1620Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,537,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: CFAP44 NM_001164496.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.09
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.157).
• BP6: Variant 3-113305051-C-T is Benign according to our data. Variant chr3-113305051-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2654040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.09 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	NM_001164496.2	MANE Select	c.4860G>A	p.Pro1620Pro	synonymous	Exon 31 of 35	NP_001157968.1	Q96MT7-2
	SPICE1-CFAP44	NR_183045.1		n.7397G>A		non_coding_transcript_exon	Exon 44 of 49
	SPICE1-CFAP44	NR_183046.1		n.7496G>A		non_coding_transcript_exon	Exon 44 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.4860G>A	p.Pro1620Pro	synonymous	Exon 31 of 35	ENSP00000377428.2	Q96MT7-2
	CFAP44	ENST00000461734.1	TSL:2	n.720G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000418795.1	H0Y896

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00669

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000499 AC: 72 AN: 144378 AF XY: 0.000441

Gnomad AFR exome AF: 0.00667

Gnomad AMR exome AF: 0.000610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000941

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000676

Gnomad OTH exome AF: 0.000234

GnomAD4 exome AF: 0.000244 AC: 338 AN: 1384890 Hom.: 0 Cov.: 30 AF XY: 0.000246 AC XY: 168 AN XY: 683372

African (AFR) AF: 0.00687 AC: 217 AN: 31586

American (AMR) AF: 0.000784 AC: 28 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35010

Middle Eastern (MID) AF: 0.000353 AC: 2 AN: 5670

European-Non Finnish (NFE) AF: 0.0000454 AC: 49 AN: 1078860

Other (OTH) AF: 0.000656 AC: 38 AN: 57918

GnomAD4 genome AF: 0.00198 AC: 301 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74464

African (AFR) AF: 0.00669 AC: 278 AN: 41558

American (AMR) AF: 0.000653 AC: 10 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00114 Hom.: 0

Bravo AF: 0.00249

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.89
PhyloP100		-4.1
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs62001862; hg19: chr3-113023898;