Variant chr19-3623716-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001080543.2(CACTIN):c.614A>G(p.Asn205Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,459,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CACTIN
NM_001080543.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.72

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CACTIN	NM_001080543.2 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/10	ENST00000429344.7
CACTIN	NM_021231.2 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/11
CACTIN	XM_011528160.3 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/8
CACTIN	XM_011528161.3 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACTIN	ENST00000429344.7 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/10	1	NM_001080543.2	P1	Q8WUQ7-1
CACTIN	ENST00000221899.7 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/12	1		P1	Q8WUQ7-1
CACTIN	ENST00000585942.5 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant, NMD_transcript_variant	2/12	1			Q8WUQ7-1
CACTIN	ENST00000248420.9 linkuse as main transcript	c.614A>G	p.Asn205Ser	missense_variant	2/11	5		P1	Q8WUQ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1459520

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

725614

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Feb 02, 2022

The c.614A>G (p.N205S) alteration is located in exon 2 (coding exon 2) of the CACTIN gene. This alteration results from a A to G substitution at nucleotide position 614, causing the asparagine (N) at amino acid position 205 to be replaced by a serine (S). 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

0.29

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

.;.;D

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.7

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.6

D;D;.

REVEL

Uncertain

0.38

Sift

Benign

0.034

D;D;.

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.86

MutPred

0.61

Loss of catalytic residue at N205 (P = 0.0297);Loss of catalytic residue at N205 (P = 0.0297);Loss of catalytic residue at N205 (P = 0.0297);

MVP

0.61

MPC

1.4

ClinPred

0.93

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.56

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