Variant 1-111348616-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181643.6(PIFO):c.359A>C(p.Lys120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIFO
NM_181643.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.430

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060883462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIFO	NM_181643.6 linkuse as main transcript	c.359A>C	p.Lys120Thr	missense_variant	4/6	ENST00000369738.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP3	ENST00000369738.9 linkuse as main transcript	c.359A>C	p.Lys120Thr	missense_variant	4/6	1	NM_181643.6	P2	Q8TCI5-1
CIMAP3	ENST00000369737.4 linkuse as main transcript	c.260A>C	p.Lys87Thr	missense_variant	3/5	2		A2	Q8TCI5-3
CIMAP3	ENST00000468395.1 linkuse as main transcript	n.276A>C		non_coding_transcript_exon_variant	1/3	2
CIMAP3	ENST00000484512.1 linkuse as main transcript	n.412A>C		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248266

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134334

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459346

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

Jan 16, 2024

The c.359A>C (p.K120T) alteration is located in exon 4 (coding exon 4) of the PIFO gene. This alteration results from a A to C substitution at nucleotide position 359, causing the lysine (K) at amino acid position 120 to be replaced by a threonine (T). 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

-0.26

BayesDel_noAF

Benign

-0.62

Cadd

Benign

5.3

Dann

Benign

0.83

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;D

REVEL

Benign

0.016

Sift

Benign

0.11

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.24

B;B

Vest4

0.15

MutPred

0.41

Loss of methylation at K120 (P = 2e-04);.;

MVP

0.067

MPC

0.14

ClinPred

0.089

GERP RS

-4.2

Varity_R

0.066

gMVP

0.36

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