chr19-3619166-C-G

Variant names:

• chr19-3619166-C-G
• rs763944157
• NM_001080543.2:c.961G>C

Variant summary

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

The NM_001080543.2(CACTIN):​c.961G>C​(p.Asp321His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D321E) 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: 7.68
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.961G>C	p.Asp321His	missense	Exon 5 of 10	NP_001074012.1	Q8WUQ7-1
	CACTIN	NM_021231.2		c.961G>C	p.Asp321His	missense	Exon 5 of 11	NP_067054.1	Q8WUQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	ENST00000429344.7	TSL:1 MANE Select	c.961G>C	p.Asp321His	missense	Exon 5 of 10	ENSP00000415078.1	Q8WUQ7-1
	CACTIN	ENST00000221899.7	TSL:1	c.961G>C	p.Asp321His	missense	Exon 5 of 12	ENSP00000221899.4	Q8WUQ7-1
	CACTIN	ENST00000585942.5	TSL:1	n.961G>C		non_coding_transcript_exon	Exon 5 of 12	ENSP00000465751.1	Q8WUQ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.016	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.83
MutPred		0.52		Loss of phosphorylation at S316 (P = 0.1164)
MVP		0.39
MPC		1.8
ClinPred		0.96	D
GERP RS		4.7
PromoterAI		-0.097	Neutral
Varity_R		0.39
gMVP		0.88
Mutation Taster		=41/59	disease causing

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: rs763944157; hg19: chr19-3619164;