rs376492815

Variant names:

• chr15-89608865-C-A
• NM_152259.4:c.2785C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89608865-C-A
• chr15-89608865-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152259.4(TICRR):​c.2785C>A​(p.Leu929Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L929V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TICRR NM_152259.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054563135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICRR	NM_152259.4	c.2785C>A	p.Leu929Ile	missense_variant	Exon 15 of 22	ENST00000268138.12	NP_689472.3
TICRR	NM_001308025.1	c.2782C>A	p.Leu928Ile	missense_variant	Exon 15 of 22		NP_001294954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICRR	ENST00000268138.12	c.2785C>A	p.Leu929Ile	missense_variant	Exon 15 of 22	5	NM_152259.4	ENSP00000268138.7
TICRR	ENST00000560985.5	c.2782C>A	p.Leu928Ile	missense_variant	Exon 15 of 22	1		ENSP00000453306.1
KIF7	ENST00000558928.1	n.*179G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3		ENSP00000504283.1
KIF7	ENST00000558928.1	n.*179G>T		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000504283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.5
DANN	Benign	0.73
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.016
Sift	Benign	0.19	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.38	B;.
Vest4		0.20
MutPred		0.12		Gain of methylation at K930 (P = 0.0485);.;
MVP		0.19
MPC		0.047
ClinPred		0.20	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.12

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: chr15-90152096;