19-3613336-G-T

Variant names:

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

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>A​(p.Pro503Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P503R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CACTIN NM_001080543.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.07217041).

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>A	p.Pro503Gln	missense	Exon 9 of 10	NP_001074012.1	Q8WUQ7-1
	CACTIN	NM_021231.2		c.1508C>A	p.Pro503Gln	missense	Exon 9 of 11	NP_067054.1	Q8WUQ7-1
	CACTIN-AS1	NR_038865.1		n.1319G>T		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>A	p.Pro503Gln	missense	Exon 9 of 10	ENSP00000415078.1	Q8WUQ7-1
	CACTIN	ENST00000221899.7	TSL:1	c.1508C>A	p.Pro503Gln	missense	Exon 9 of 12	ENSP00000221899.4	Q8WUQ7-1
	CACTIN	ENST00000592721.5	TSL:1	c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	ENSP00000467149.1	K7ENY9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.65
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.89
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.0080
Sift	Benign	0.36	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.22		Loss of glycosylation at P503 (P = 0.0245)
MVP		0.043
MPC		0.58
ClinPred		0.38	T
GERP RS		0.41
PromoterAI		-0.015	Neutral
Varity_R		0.036
gMVP		0.51
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;