rs758119857

Variant names:

• chr19-3613336-G-C
• rs758119857
• NM_001080543.2:c.1508C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-3613336-G-C
• chr19-3613336-G-A
• chr19-3613336-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080543.2(CACTIN):​c.1508C>G​(p.Pro503Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,367,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000022 (0 hom.)
• Consequence: CACTIN NM_001080543.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.893
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08212489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080543.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	NM_001080543.2	MANE Select	c.1508C>G	p.Pro503Arg	missense	Exon 9 of 10	NP_001074012.1	Q8WUQ7-1
	CACTIN	NM_021231.2		c.1508C>G	p.Pro503Arg	missense	Exon 9 of 11	NP_067054.1	Q8WUQ7-1
	CACTIN-AS1	NR_038865.1		n.1319G>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	ENST00000429344.7	TSL:1 MANE Select	c.1508C>G	p.Pro503Arg	missense	Exon 9 of 10	ENSP00000415078.1	Q8WUQ7-1
	CACTIN	ENST00000221899.7	TSL:1	c.1508C>G	p.Pro503Arg	missense	Exon 9 of 12	ENSP00000221899.4	Q8WUQ7-1
	CACTIN	ENST00000592721.5	TSL:1	c.104C>G	p.Pro35Arg	missense	Exon 2 of 4	ENSP00000467149.1	K7ENY9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000825 AC: 1 AN: 121140 AF XY: 0.0000150

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000200

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367846 Hom.: 0 Cov.: 56 AF XY: 0.00000445 AC XY: 3 AN XY: 674310

African (AFR) AF: 0.00 AC: 0 AN: 30016

American (AMR) AF: 0.00 AC: 0 AN: 31988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 74894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1072404

Other (OTH) AF: 0.00 AC: 0 AN: 56942

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.89
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.013
Sift	Benign	0.22	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.23
MutPred		0.23		Loss of glycosylation at P503 (P = 0.0245)
MVP		0.043
MPC		0.66
ClinPred		0.057	T
GERP RS		0.41
PromoterAI		-0.0048	Neutral
Varity_R		0.049
gMVP		0.60
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs758119857; hg19: chr19-3613334;