dbSNP rs12977510: CACTIN:p.Pro490Thr (chr19-3613474-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080543.2(CACTIN):c.1468C>A(p.Pro490Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACTIN
NM_001080543.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Publications

2 publications found

Variant links:

Genes affected

CACTIN (HGNC:29938): (cactin, spliceosome C complex subunit) Enables RNA binding activity. Involved in several processes, including cellular response to cytokine stimulus; negative regulation of cytokine production; and negative regulation of signal transduction. Located in cytosol and nuclear speck. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

CACTIN links:

CACTIN-AS1 (HGNC:31391): (CACTIN antisense RNA 1)

CACTIN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06555599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACTIN	NM_001080543.2 link	c.1468C>A	p.Pro490Thr	missense_variant	Exon 8 of 10	ENST00000429344.7	NP_001074012.1	Q8WUQ7-1
CACTIN	NM_021231.2 link	c.1468C>A	p.Pro490Thr	missense_variant	Exon 8 of 11		NP_067054.1	Q8WUQ7-1
CACTIN-AS1	NR_038865.1 link	n.1457G>T		non_coding_transcript_exon_variant	Exon 4 of 4
CACTIN	XM_011528160.3 link	c.*120C>A		downstream_gene_variant			XP_011526462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7 link	c.1468C>A	p.Pro490Thr	missense_variant	Exon 8 of 10	1	NM_001080543.2	ENSP00000415078.1		Q8WUQ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1427606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707968

African (AFR)

AF:

0.00

AC:

AN:

32988

American (AMR)

AF:

0.00

AC:

AN:

40710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25606

East Asian (EAS)

AF:

0.00

AC:

AN:

38324

South Asian (SAS)

AF:

0.00

AC:

AN:

82392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099516

Other (OTH)

AF:

0.00

AC:

AN:

59304

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0091

T;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.71

.;.;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L

PhyloP100

3.5

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.40

N;N;.

REVEL

Benign

0.073

Sift

Benign

0.77

T;T;.

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.15

MutPred

0.29

Gain of phosphorylation at P490 (P = 0.0111);Gain of phosphorylation at P490 (P = 0.0111);Gain of phosphorylation at P490 (P = 0.0111);

MVP

0.043

MPC

0.70

ClinPred

0.41

GERP RS

1.8

PromoterAI

0.0088

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.67

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over