chr1-111346957-T-C

Position:

• chr1-111346957-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

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 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	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	c.67T>C	p.Phe23Leu	missense_variant	2/6	1	NM_181643.6	P2
CIMAP3	ENST00000369737.4	c.67T>C	p.Phe23Leu	missense_variant	2/5	2		A2
CIMAP3	ENST00000484512.1	n.120T>C		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

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: 6 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

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: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

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	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	0.96	D;D
PrimateAI	Uncertain	0.63	T
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	D
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

Other links and lift over

dbSNP: rs1650507407; hg19: chr1-111889579;