chr15-89576139-C-T

Position:

• chr15-89576139-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152259.4(TICRR):​c.553C>T​(p.Pro185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: TICRR NM_152259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0891327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TICRR	NM_152259.4	c.553C>T	p.Pro185Ser	missense_variant	1/22	ENST00000268138.12
TICRR	NM_001308025.1	c.553C>T	p.Pro185Ser	missense_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TICRR	ENST00000268138.12	c.553C>T	p.Pro185Ser	missense_variant	1/22	5	NM_152259.4	A2
TICRR	ENST00000560985.5	c.553C>T	p.Pro185Ser	missense_variant	1/22	1		P4
	ENST00000559041.1	n.48-15364C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Apr 25, 2022

The c.553C>T (p.P185S) alteration is located in exon 1 (coding exon 1) of the TICRR gene. This alteration results from a C to T substitution at nucleotide position 553, causing the proline (P) at amino acid position 185 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.0048	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.064
Sift	Benign	0.095	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.058	B;.
Vest4		0.25
MutPred		0.24		Loss of glycosylation at P185 (P = 0.0382);Loss of glycosylation at P185 (P = 0.0382);
MVP		0.12
MPC		0.030
ClinPred		0.15	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.44

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: chr15-90119370;