NM_032848.3:c.493C>T

Variant names:

• chr12-113191500-C-T
• NM_032848.3:c.493C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032848.3(RITA1):​c.493C>T​(p.His165Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RITA1 NM_032848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

Genes affected

RITA1 (HGNC:25925): (RBPJ interacting and tubulin associated 1) Enables tubulin binding activity. Involved in negative regulation of Notch signaling pathway and nuclear export. Located in centrosome; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000257286 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2940533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032848.3. 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
	RITA1	NM_032848.3	MANE Select	c.493C>T	p.His165Tyr	missense	Exon 4 of 4	NP_116237.1	Q96K30-1
	RITA1	NM_001286215.2		c.565C>T	p.His189Tyr	missense	Exon 3 of 3	NP_001273144.1	Q96K30-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RITA1	ENST00000548278.2	TSL:1 MANE Select	c.493C>T	p.His165Tyr	missense	Exon 4 of 4	ENSP00000449841.1	Q96K30-1
	RITA1	ENST00000552495.1	TSL:2	c.565C>T	p.His189Tyr	missense	Exon 3 of 3	ENSP00000448680.1	Q96K30-3
	RITA1	ENST00000549621.5	TSL:2	c.493C>T	p.His165Tyr	missense	Exon 4 of 4	ENSP00000448289.1	Q96K30-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.20
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.1
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.20		Gain of catalytic residue at G168 (P = 0.0014)
MVP		0.27
MPC		0.83
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.30
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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: chr12-113629305;