3-119703120-G-C

Position:

chr3-119703120-G-C

Variant summary

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

The NM_033364.4(CFAP91):c.22G>C(p.Glu8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,565,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CFAP91
NM_033364.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.375

Variant links:

Genes affected

CFAP91 (HGNC:24010): (cilia and flagella associated protein 91) Predicted to be involved in cilium movement. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. Implicated in spermatogenic failure 51. [provided by Alliance of Genome Resources, Apr 2022]

CFAP91 links:

ENSG00000285585 (HGNC:):

ENSG00000285585 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=0.020679265).

BP6

Variant 3-119703120-G-C is Benign according to our data. Variant chr3-119703120-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2601622.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP91	NM_033364.4 linkuse as main transcript	c.22G>C	p.Glu8Gln	missense_variant	1/18	ENST00000273390.9	NP_203528.3	Q7Z4T9-7
CFAP91	NM_001320316.2 linkuse as main transcript	c.-88G>C		5_prime_UTR_variant	1/18		NP_001307245.2	Q7Z4T9
CFAP91	NM_001320317.2 linkuse as main transcript	c.-88G>C		5_prime_UTR_variant	1/17		NP_001307246.2	Q7Z4T9-3
CFAP91	NM_001320318.2 linkuse as main transcript	c.-122G>C		5_prime_UTR_variant	1/16		NP_001307247.2	Q7Z4T9-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP91	ENST00000273390.9 linkuse as main transcript	c.22G>C	p.Glu8Gln	missense_variant	1/18	1	NM_033364.4	ENSP00000273390.5		Q7Z4T9-7
ENSG00000285585	ENST00000648112.1 linkuse as main transcript	c.22G>C	p.Glu8Gln	missense_variant	1/18			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

175688

Hom.:

AF XY:

0.0000214

AC XY:

AN XY:

93672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000408

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000142

AC:

201

AN:

1413226

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

100

AN XY:

698666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.29

DANN

Benign

0.54

DEOGEN2

Benign

0.00074

T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.50

.;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.080

N;N;.

REVEL

Benign

0.010

Sift

Benign

0.94

T;T;.

Sift4G

Benign

0.59

T;T;.

Polyphen

0.015

.;B;.

Vest4

0.14

MutPred

0.22

Loss of catalytic residue at E8 (P = 0.0603);Loss of catalytic residue at E8 (P = 0.0603);Loss of catalytic residue at E8 (P = 0.0603);

MVP

0.030

MPC

0.13

ClinPred

0.015

GERP RS

-1.9

Varity_R

0.070

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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