rs12977510

Positions:

• chr19-3613474-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/20 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46

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

ACMG classification

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=0.06555599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACTIN	NM_001080543.2	c.1468C>A	p.Pro490Thr	missense_variant	8/10	ENST00000429344.7
CACTIN-AS1	NR_038865.1	n.1457G>T		non_coding_transcript_exon_variant	4/4
CACTIN	NM_021231.2	c.1468C>A	p.Pro490Thr	missense_variant	8/11
CACTIN	XM_011528160.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACTIN	ENST00000429344.7	c.1468C>A	p.Pro490Thr	missense_variant	8/10	1	NM_001080543.2	P1
CACTIN-AS1	ENST00000592274.1	n.1457G>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427606 Hom.: 0 Cov.: 71 AF XY: 0.00 AC XY: 0 AN XY: 707968

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
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	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.65	T
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	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.67

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

Other links and lift over

dbSNP: rs12977510; hg19: chr19-3613472;