chr12-113191465-C-T

Variant names:

• chr12-113191465-C-T
• rs780914706
• NM_032848.3:c.458C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032848.3(RITA1):​c.458C>T​(p.Ser153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,604,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RITA1 NM_032848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16633573).

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.458C>T	p.Ser153Leu	missense	Exon 4 of 4	NP_116237.1	Q96K30-1
	RITA1	NM_001286215.2		c.530C>T	p.Ser177Leu	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.458C>T	p.Ser153Leu	missense	Exon 4 of 4	ENSP00000449841.1	Q96K30-1
	RITA1	ENST00000552495.1	TSL:2	c.530C>T	p.Ser177Leu	missense	Exon 3 of 3	ENSP00000448680.1	Q96K30-3
	RITA1	ENST00000549621.5	TSL:2	c.458C>T	p.Ser153Leu	missense	Exon 4 of 4	ENSP00000448289.1	Q96K30-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000285 AC: 7 AN: 245666 AF XY: 0.0000301

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1451916 Hom.: 0 Cov.: 31 AF XY: 0.0000264 AC XY: 19 AN XY: 720372

African (AFR) AF: 0.000120 AC: 4 AN: 33334

American (AMR) AF: 0.0000677 AC: 3 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000253 AC: 28 AN: 1104814

Other (OTH) AF: 0.0000669 AC: 4 AN: 59808

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000593 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Benign	0.047
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.2
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.17		Gain of catalytic residue at S153 (P = 5e-04)
MVP		0.19
MPC		0.29
ClinPred		0.75	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.17
Mutation Taster		=97/3	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

dbSNP: rs780914706; hg19: chr12-113629270; COSMIC: COSV55321046; COSMIC: COSV55321046;