Variant 3-113330197-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001164496.2(CFAP44):c.4087G>A(p.Val1363Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,537,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1363L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

CFAP44
NM_001164496.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.22

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004479617).

BP6

Variant 3-113330197-C-T is Benign according to our data. Variant chr3-113330197-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 739316.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP44	NM_001164496.2 linkuse as main transcript	c.4087G>A	p.Val1363Met	missense_variant	26/35	ENST00000393845.9
LOC127898559	NR_183046.1 linkuse as main transcript	n.6723G>A		non_coding_transcript_exon_variant	39/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP44	ENST00000393845.9 linkuse as main transcript	c.4087G>A	p.Val1363Met	missense_variant	26/35	5	NM_001164496.2	P2	Q96MT7-2

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000343

AC:

AN:

145826

Hom.:

AF XY:

0.000298

AC XY:

AN XY:

77308

show subpopulations

Gnomad AFR exome

AF:

0.00487

Gnomad AMR exome

AF:

0.000325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000889

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

190

AN:

1384730

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

683180

show subpopulations

Gnomad4 AFR exome

AF:

0.00443

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000380

Gnomad4 FIN exome

AF:

0.0000568

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.000396

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152286

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00474

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.00147

ESP6500AA

AF:

0.00434

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000287

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely 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

Benign

0.094

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.11

DANN

Benign

0.76

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.57

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.23

REVEL

Benign

0.020

Sift

Benign

0.21

Sift4G

Benign

0.16

Vest4

0.14

MVP

0.067

MPC

0.10

ClinPred

0.013

GERP RS

-11

Varity_R

0.037

gMVP

0.18

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