Variant chr19-3623965-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080543.2(CACTIN):c.365G>A(p.Gly122Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACTIN
NM_001080543.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.564

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 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=0.047769696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CACTIN	NM_001080543.2 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant	2/10	ENST00000429344.7	NP_001074012.1
CACTIN	NM_021231.2 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant	2/11		NP_067054.1
CACTIN	XM_011528160.3 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant	2/8		XP_011526462.1
CACTIN	XM_011528161.3 linkuse as main transcript	c.365G>A	p.Gly122Glu	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.365G>A	p.Gly122Glu	missense_variant	2/10	1	NM_001080543.2	ENSP00000415078	P1	Q8WUQ7-1
CACTIN	ENST00000221899.7 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant	2/12	1		ENSP00000221899	P1	Q8WUQ7-1
CACTIN	ENST00000585942.5 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant, NMD_transcript_variant	2/12	1		ENSP00000465751		Q8WUQ7-1
CACTIN	ENST00000248420.9 linkuse as main transcript	c.365G>A	p.Gly122Glu	missense_variant	2/11	5		ENSP00000248420	P1	Q8WUQ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1451222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000835

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

Apr 23, 2024

The c.365G>A (p.G122E) alteration is located in exon 2 (coding exon 2) of the CACTIN gene. This alteration results from a G to A substitution at nucleotide position 365, causing the glycine (G) at amino acid position 122 to be replaced by a glutamic acid (E). 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

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.17

DANN

Benign

0.81

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.38

.;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.11

N;N;.

REVEL

Benign

0.011

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.87

T;T;T

Polyphen

0.018

B;B;B

Vest4

0.094

MutPred

0.18

Loss of MoRF binding (P = 0.0179);Loss of MoRF binding (P = 0.0179);Loss of MoRF binding (P = 0.0179);

MVP

0.068

MPC

0.81

ClinPred

0.033

GERP RS

-1.4

Varity_R

0.027

gMVP

0.038

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