15-89619775-C-G

Variant summary

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

The NM_152259.4(TICRR):​c.3087C>G​(p.Phe1029Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TICRR
NM_152259.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
TICRRNM_152259.4 linkc.3087C>G p.Phe1029Leu missense_variant Exon 18 of 22 ENST00000268138.12 NP_689472.3 Q7Z2Z1-1
TICRRNM_001308025.1 linkc.3084C>G p.Phe1028Leu missense_variant Exon 18 of 22 NP_001294954.1 Q7Z2Z1-2
KIF7XM_047432481.1 linkc.3848-1580G>C intron_variant Intron 19 of 19 XP_047288437.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TICRRENST00000268138.12 linkc.3087C>G p.Phe1029Leu missense_variant Exon 18 of 22 5 NM_152259.4 ENSP00000268138.7 Q7Z2Z1-1
TICRRENST00000560985.5 linkc.3084C>G p.Phe1028Leu missense_variant Exon 18 of 22 1 ENSP00000453306.1 Q7Z2Z1-2
KIF7ENST00000558928.1 linkn.179-1580G>C intron_variant Intron 1 of 2 3 ENSP00000504283.1 A0A7I2V527

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461726
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3087C>G (p.F1029L) alteration is located in exon 18 (coding exon 18) of the TICRR gene. This alteration results from a C to G substitution at nucleotide position 3087, causing the phenylalanine (F) at amino acid position 1029 to be replaced by a leucine (L). 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
Pathogenic
0.87
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.076
T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.16
T;T
Polyphen
1.0
D;.
Vest4
0.60
MutPred
0.14
Gain of MoRF binding (P = 0.1817);.;
MVP
0.40
MPC
0.21
ClinPred
0.99
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.77
gMVP
0.35

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: chr15-90163006; API