Variant 3-119708658-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033364.4(CFAP91):c.427T>C(p.Tyr143His) variant causes a missense change. The variant allele was found at a frequency of 0.0000195 in 1,586,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CFAP91
NM_033364.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37758785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP91	NM_033364.4 linkuse as main transcript	c.427T>C	p.Tyr143His	missense_variant	4/18	ENST00000273390.9	NP_203528.3	Q7Z4T9-7
CFAP91	NM_001320316.2 linkuse as main transcript	c.367T>C	p.Tyr123His	missense_variant	4/18		NP_001307245.2	Q7Z4T9
CFAP91	NM_001320317.2 linkuse as main transcript	c.241T>C	p.Tyr81His	missense_variant	3/17		NP_001307246.2	Q7Z4T9-3
CFAP91	NM_001320318.2 linkuse as main transcript	c.49T>C	p.Tyr17His	missense_variant	2/16		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.427T>C	p.Tyr143His	missense_variant	4/18	1	NM_033364.4	ENSP00000273390.5		Q7Z4T9-7
ENSG00000285585	ENST00000648112.1 linkuse as main transcript	c.427T>C	p.Tyr143His	missense_variant	4/18			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244332

Hom.:

AF XY:

0.0000529

AC XY:

AN XY:

132298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000448

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000188

AC:

AN:

1434144

Hom.:

Cov.:

AF XY:

0.0000238

AC XY:

AN XY:

714476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000685

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000769

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000577

AC:

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

Oct 10, 2023

The c.427T>C (p.Y143H) alteration is located in exon 4 (coding exon 4) of the MAATS1 gene. This alteration results from a T to C substitution at nucleotide position 427, causing the tyrosine (Y) at amino acid position 143 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.56

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.6

D;D;.

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.54

P;D;.

Vest4

0.65

MutPred

0.75

Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);Gain of disorder (P = 0.0461);

MVP

0.55

MPC

0.36

ClinPred

0.76

GERP RS

6.0

Varity_R

0.52

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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