Variant 1-111346957-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_181643.6(PIFO):c.67T>C(p.Phe23Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PIFO
NM_181643.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

PIFO (HGNC:):

PIFO links:

CIMAP3 (HGNC:27009): (ciliary microtubule associated protein 3) Enables cytoskeletal protein binding activity and enzyme binding activity. Involved in positive regulation of kinase activity. Predicted to be located in trans-Golgi network. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIFO	NM_181643.6 linkuse as main transcript	c.67T>C	p.Phe23Leu	missense_variant	2/6	ENST00000369738.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP3	ENST00000369738.9 linkuse as main transcript	c.67T>C	p.Phe23Leu	missense_variant	2/6	1	NM_181643.6	P2	Q8TCI5-1
CIMAP3	ENST00000369737.4 linkuse as main transcript	c.67T>C	p.Phe23Leu	missense_variant	2/5	2		A2	Q8TCI5-3
CIMAP3	ENST00000484512.1 linkuse as main transcript	n.120T>C		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0077

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Benign

0.15

Sift

Benign

0.091

T;T

Sift4G

Benign

0.099

T;T

Polyphen

1.0

D;D

Vest4

0.80

MutPred

0.65

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.43

MPC

0.52

ClinPred

0.99

GERP RS

5.1

Varity_R

0.33

gMVP

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over