Variant 3-113326478-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001164496.2(CFAP44):c.4483C>T(p.Arg1495Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,515,284 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 33 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.82

Variant links:

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 links:

LOC127898559 (HGNC:):

LOC127898559 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041759014).

BP6

Variant 3-113326478-G-A is Benign according to our data. Variant chr3-113326478-G-A is described in ClinVar as [Benign]. Clinvar id is 791437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00868 (1321/152174) while in subpopulation AFR AF= 0.0214 (890/41550). AF 95% confidence interval is 0.0203. There are 16 homozygotes in gnomad4. There are 644 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP44	NM_001164496.2 linkuse as main transcript	c.4483C>T	p.Arg1495Trp	missense_variant	28/35	ENST00000393845.9
LOC127898559	NR_183046.1 linkuse as main transcript	n.7119C>T		non_coding_transcript_exon_variant	41/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP44	ENST00000393845.9 linkuse as main transcript	c.4483C>T	p.Arg1495Trp	missense_variant	28/35	5	NM_001164496.2	P2	Q96MT7-2
CFAP44	ENST00000461734.1 linkuse as main transcript	c.346C>T	p.Arg116Trp	missense_variant, NMD_transcript_variant	2/10	2

Frequencies

GnomAD3 genomes

AF:

0.00866

AC:

1317

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000944

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00405

AC:

515

AN:

127092

Hom.:

AF XY:

0.00370

AC XY:

249

AN XY:

67244

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00274

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.00408

Gnomad OTH exome

AF:

0.00411

GnomAD4 exome

AF:

0.00399

AC:

5435

AN:

1363110

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2632

AN XY:

671636

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00328

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.000170

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.00378

Gnomad4 OTH exome

AF:

0.00506

GnomAD4 genome

AF:

0.00868

AC:

1321

AN:

152174

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

644

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.00661

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000944

Gnomad4 NFE

AF:

0.00416

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.0231

AC:

ESP6500EA

AF:

0.00377

AC:

ExAC

AF:

0.00459

AC:

108

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Benign

0.019

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.52

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Vest4

0.22

MVP

0.42

MPC

0.25

ClinPred

0.025

GERP RS

4.3

Varity_R

0.29

gMVP

0.24

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over