chr3-113291704-T-C

Variant names:

• chr3-113291704-T-C
• rs369806513
• NM_001164496.2:c.5418A>G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001164496.2(CFAP44):​c.5418A>G​(p.Arg1806Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,536,908 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: CFAP44 NM_001164496.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.417

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-113291704-T-C is Benign according to our data. Variant chr3-113291704-T-C is described in ClinVar as [Benign]. Clinvar id is 717618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.417 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2	c.5418A>G	p.Arg1806Arg	synonymous_variant	Exon 35 of 35	ENST00000393845.9	NP_001157968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP44	ENST00000393845.9	c.5418A>G	p.Arg1806Arg	synonymous_variant	Exon 35 of 35	5	NM_001164496.2	ENSP00000377428.2

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00186 AC: 271 AN: 146068 Hom.: 1 AF XY: 0.00184 AC XY: 143 AN XY: 77616

Gnomad AFR exome AF: 0.000630

Gnomad AMR exome AF: 0.000244

Gnomad ASJ exome AF: 0.00628

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000660

Gnomad FIN exome AF: 0.00396

Gnomad NFE exome AF: 0.00251

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00264 AC: 3649 AN: 1384576 Hom.: 8 Cov.: 34 AF XY: 0.00247 AC XY: 1687 AN XY: 683196

Gnomad4 AFR exome AF: 0.000285

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.00735

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000581

Gnomad4 FIN exome AF: 0.00424

Gnomad4 NFE exome AF: 0.00285

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74490

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.00257

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00255 Hom.: 1

Bravo AF: 0.00153

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CFAP44-related disorder Benign:1

Feb 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs369806513; hg19: chr3-113010551;