15-89575671-C-G

Variant names:

• chr15-89575671-C-G
• NM_152259.4:c.85C>G

Variant summary

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

The NM_152259.4(TICRR):​c.85C>G​(p.Arg29Gly) 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 pathogenic 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: 1.53

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]

ENSG00000259713 (HGNC:):

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, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICRR	NM_152259.4	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 22	ENST00000268138.12	NP_689472.3
TICRR	NM_001308025.1	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 22		NP_001294954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICRR	ENST00000268138.12	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 22	5	NM_152259.4	ENSP00000268138.7
TICRR	ENST00000560985.5	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 22	1		ENSP00000453306.1
ENSG00000259713	ENST00000559041.1	n.48-15832C>G		intron_variant	Intron 1 of 1	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

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.85C>G (p.R29G) alteration is located in exon 1 (coding exon 1) of the TICRR gene. This alteration results from a C to G substitution at nucleotide position 85, causing the arginine (R) at amino acid position 29 to be replaced by a glycine (G). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.16
Sift	Benign	0.037	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.84
MutPred		0.38		Loss of methylation at R29 (P = 0.0288);Loss of methylation at R29 (P = 0.0288);
MVP		0.35
MPC		2.4
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.75

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: chr15-90118902;