Variant 3-119707417-G-A 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.215G>A(p.Arg72Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,556,010 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 30)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CFAP91
NM_033364.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

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=0.068240255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP91	NM_033364.4 linkuse as main transcript	c.215G>A	p.Arg72Lys	missense_variant	3/18	ENST00000273390.9	NP_203528.3	Q7Z4T9-7
CFAP91	NM_001320316.2 linkuse as main transcript	c.155G>A	p.Arg52Lys	missense_variant	3/18		NP_001307245.2	Q7Z4T9
CFAP91	NM_001320317.2 linkuse as main transcript	c.29G>A	p.Arg10Lys	missense_variant	2/17		NP_001307246.2	Q7Z4T9-3
CFAP91	NM_001320318.2 linkuse as main transcript	c.-19-1174G>A		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.215G>A	p.Arg72Lys	missense_variant	3/18	1	NM_033364.4	ENSP00000273390.5		Q7Z4T9-7
ENSG00000285585	ENST00000648112.1 linkuse as main transcript	c.215G>A	p.Arg72Lys	missense_variant	3/18			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000879

AC:

AN:

238874

Hom.:

AF XY:

0.0000775

AC XY:

AN XY:

129086

show subpopulations

Gnomad AFR exome

AF:

0.000504

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000472

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1404018

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

693894

show subpopulations

Gnomad4 AFR exome

AF:

0.000368

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.000138

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000969

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Jul 09, 2024

The c.215G>A (p.R72K) alteration is located in exon 3 (coding exon 3) of the MAATS1 gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0048

T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.56

.;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.25

N;N;.

REVEL

Benign

0.059

Sift

Benign

0.74

T;T;.

Sift4G

Benign

0.67

T;T;.

Polyphen

0.43

B;P;.

Vest4

0.085

MVP

0.26

MPC

0.14

ClinPred

0.025

GERP RS

3.0

Varity_R

0.053

gMVP

0.42

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