1-111346936-A-G

Position:

• chr1-111346936-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181643.6(PIFO):​c.46A>G​(p.Thr16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIFO NM_181643.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0170

Genes affected

PIFO (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIFO	NM_181643.6	c.46A>G	p.Thr16Ala	missense_variant	2/6	ENST00000369738.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP3	ENST00000369738.9	c.46A>G	p.Thr16Ala	missense_variant	2/6	1	NM_181643.6	P2
CIMAP3	ENST00000369737.4	c.46A>G	p.Thr16Ala	missense_variant	2/5	2		A2
CIMAP3	ENST00000484512.1	n.99A>G		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.46A>G (p.T16A) alteration is located in exon 2 (coding exon 2) of the PIFO gene. This alteration results from a A to G substitution at nucleotide position 46, causing the threonine (T) at amino acid position 16 to be replaced by an alanine (A). 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	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0082	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.82	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	D;D
Vest4		0.51
MutPred		0.33		Gain of catalytic residue at T16 (P = 0.0561);Gain of catalytic residue at T16 (P = 0.0561);
MVP		0.28
MPC		0.39
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.16
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-111889558;