NM_152259.4:c.85C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICRR	NM_152259.4	MANE Select	c.85C>G	p.Arg29Gly	missense	Exon 1 of 22	NP_689472.3
	TICRR	NM_001308025.1		c.85C>G	p.Arg29Gly	missense	Exon 1 of 22	NP_001294954.1	Q7Z2Z1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICRR	ENST00000268138.12	TSL:5 MANE Select	c.85C>G	p.Arg29Gly	missense	Exon 1 of 22	ENSP00000268138.7	Q7Z2Z1-1
	TICRR	ENST00000560985.5	TSL:1	c.85C>G	p.Arg29Gly	missense	Exon 1 of 22	ENSP00000453306.1	Q7Z2Z1-2
	TICRR	ENST00000929580.1		c.85C>G	p.Arg29Gly	missense	Exon 1 of 21	ENSP00000599639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.16
Sift	Benign	0.037	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.38		Loss of methylation at R29 (P = 0.0288)
MVP		0.35
MPC		2.4
ClinPred		0.98	D
GERP RS		4.8
PromoterAI		0.16	Neutral
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

Other links and lift over

hg19: chr15-90118902;