rs1316267550

Variant names:

• chr15-89575956-C-G
• rs1316267550
• NM_152259.4:c.370C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152259.4(TICRR):​c.370C>G​(p.Pro124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TICRR NM_152259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24478984).

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.370C>G	p.Pro124Ala	missense	Exon 1 of 22	NP_689472.3
	TICRR	NM_001308025.1		c.370C>G	p.Pro124Ala	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.370C>G	p.Pro124Ala	missense	Exon 1 of 22	ENSP00000268138.7	Q7Z2Z1-1
	TICRR	ENST00000560985.5	TSL:1	c.370C>G	p.Pro124Ala	missense	Exon 1 of 22	ENSP00000453306.1	Q7Z2Z1-2
	TICRR	ENST00000929580.1		c.370C>G	p.Pro124Ala	missense	Exon 1 of 21	ENSP00000599639.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000449 AC: 1 AN: 222702 AF XY: 0.00000814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450126 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720870

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.00 AC: 0 AN: 43350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39218

South Asian (SAS) AF: 0.00 AC: 0 AN: 85020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107938

Other (OTH) AF: 0.00 AC: 0 AN: 59966

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

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	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.030
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Polyphen		0.86	P
Vest4		0.43
MutPred		0.31		Gain of helix (P = 0.027)
MVP		0.27
MPC		1.8
ClinPred		0.81	D
GERP RS		3.8
PromoterAI		-0.0081	Neutral
Varity_R		0.13
gMVP		0.68

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

dbSNP: rs1316267550; hg19: chr15-90119187;