Variant 3-119706874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033364.4(CFAP91):c.190C>T(p.Arg64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CFAP91
NM_033364.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.411

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19423237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP91	NM_033364.4 linkuse as main transcript	c.190C>T	p.Arg64Cys	missense_variant	2/18	ENST00000273390.9	NP_203528.3	Q7Z4T9-7
CFAP91	NM_001320316.2 linkuse as main transcript	c.130C>T	p.Arg44Cys	missense_variant	2/18		NP_001307245.2	Q7Z4T9
CFAP91	NM_001320317.2 linkuse as main transcript	c.16-530C>T		intron_variant			NP_001307246.2	Q7Z4T9-3
CFAP91	NM_001320318.2 linkuse as main transcript	c.-19-1717C>T		intron_variant			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.190C>T	p.Arg64Cys	missense_variant	2/18	1	NM_033364.4	ENSP00000273390.5		Q7Z4T9-7
ENSG00000285585	ENST00000648112.1 linkuse as main transcript	c.190C>T	p.Arg64Cys	missense_variant	2/18			ENSP00000497876.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251400

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461046

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.190C>T (p.R64C) alteration is located in exon 2 (coding exon 2) of the MAATS1 gene. This alteration results from a C to T substitution at nucleotide position 190, causing the arginine (R) at amino acid position 64 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.87

.;D;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.85

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

N;D;.

REVEL

Benign

0.23

Sift

Benign

0.072

T;D;.

Sift4G

Uncertain

0.059

T;T;.

Polyphen

1.0

D;D;.

Vest4

0.20

MutPred

0.42

Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);

MVP

0.39

MPC

0.59

ClinPred

0.85

GERP RS

0.65

Varity_R

0.081

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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