chr3-113304042-G-A

Variant names:

• chr3-113304042-G-A
• rs185086524
• NM_001164496.2:c.4951C>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001164496.2(CFAP44):​c.4951C>T​(p.Arg1651Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,537,208 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (5 hom.)
• Consequence: CFAP44 NM_001164496.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.17

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012668788).
• BP6: Variant 3-113304042-G-A is Benign according to our data. Variant chr3-113304042-G-A is described in ClinVar as [Benign]. Clinvar id is 770705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP44	NM_001164496.2	c.4951C>T	p.Arg1651Trp	missense_variant	Exon 32 of 35	ENST00000393845.9	NP_001157968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP44	ENST00000393845.9	c.4951C>T	p.Arg1651Trp	missense_variant	Exon 32 of 35	5	NM_001164496.2	ENSP00000377428.2
CFAP44	ENST00000461734.1	n.811C>T		non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000418795.1
CFAP44	ENST00000465510.1	n.236C>T		non_coding_transcript_exon_variant	Exon 1 of 3	4
CFAP44	ENST00000489244.1	n.25C>T		non_coding_transcript_exon_variant	Exon 1 of 4	5		ENSP00000418257.1

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 152038 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00219 AC: 318 AN: 145032 Hom.: 0 AF XY: 0.00229 AC XY: 177 AN XY: 77268

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.00268

Gnomad ASJ exome AF: 0.00499

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000176

Gnomad FIN exome AF: 0.00343

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.00232

GnomAD4 exome AF: 0.00287 AC: 3976 AN: 1385052 Hom.: 5 Cov.: 36 AF XY: 0.00276 AC XY: 1883 AN XY: 683450

Gnomad4 AFR exome AF: 0.000665

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.00477

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000391

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.00317

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152156 Hom.: 1 Cov.: 33 AF XY: 0.00202 AC XY: 150 AN XY: 74368

Gnomad4 AFR AF: 0.000723

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00291 Hom.: 1

Bravo AF: 0.00238

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00217 AC: 3

ESP6500EA AF: 0.00126 AC: 4

ExAC AF: 0.00146 AC: 34

Asia WGS AF: 0.000867 AC: 3 AN: 3476

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

Sep 07, 2024

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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Pathogenic	1.0
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.052	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.091
Sift	Benign	0.048	D
Sift4G	Uncertain	0.026	D
Vest4		0.40
MVP		0.34
MPC		0.19
ClinPred		0.018	T
GERP RS		3.8
Varity_R		0.11
gMVP		0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs185086524; hg19: chr3-113022889;