Variant 19-3623948-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080543.2(CACTIN):c.382C>T(p.Arg128Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,602,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

CACTIN
NM_001080543.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14378864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CACTIN	NM_001080543.2 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/10	ENST00000429344.7	NP_001074012.1
CACTIN	NM_021231.2 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/11		NP_067054.1
CACTIN	XM_011528160.3 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/8		XP_011526462.1
CACTIN	XM_011528161.3 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/7		XP_011526463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/10	1	NM_001080543.2	ENSP00000415078	P1	Q8WUQ7-1
CACTIN	ENST00000221899.7 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/12	1		ENSP00000221899	P1	Q8WUQ7-1
CACTIN	ENST00000585942.5 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant, NMD_transcript_variant	2/12	1		ENSP00000465751		Q8WUQ7-1
CACTIN	ENST00000248420.9 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/11	5		ENSP00000248420	P1	Q8WUQ7-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000305

AC:

AN:

229632

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127024

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000675

Gnomad NFE exome

AF:

0.0000575

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000531

AC:

AN:

1450008

Hom.:

Cov.:

AF XY:

0.0000485

AC XY:

AN XY:

721460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.0000447

Gnomad4 NFE exome

AF:

0.0000631

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000791

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.382C>T (p.R128W) alteration is located in exon 2 (coding exon 2) of the CACTIN gene. This alteration results from a C to T substitution at nucleotide position 382, causing the arginine (R) at amino acid position 128 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

N;N;.

REVEL

Benign

0.068

Sift

Uncertain

0.023

D;D;.

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.95

P;P;P

Vest4

0.33

MVP

0.14

MPC

0.65

ClinPred

0.11

GERP RS

-1.6

Varity_R

0.056

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over