19-3613220-T-C

Variant names:

• chr19-3613220-T-C
• NM_001080543.2:c.1624A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080543.2(CACTIN):​c.1624A>G​(p.Met542Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: CACTIN NM_001080543.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13533509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACTIN	NM_001080543.2	c.1624A>G	p.Met542Val	missense_variant	Exon 9 of 10	ENST00000429344.7	NP_001074012.1
CACTIN	NM_021231.2	c.1624A>G	p.Met542Val	missense_variant	Exon 9 of 11		NP_067054.1
CACTIN-AS1	NR_038865.1	n.1203T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7	c.1624A>G	p.Met542Val	missense_variant	Exon 9 of 10	1	NM_001080543.2	ENSP00000415078.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1624A>G (p.M542V) alteration is located in exon 9 (coding exon 9) of the CACTIN gene. This alteration results from a A to G substitution at nucleotide position 1624, causing the methionine (M) at amino acid position 542 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.59
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	.;.;D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.33	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.52	T;T;.
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.34
MutPred		0.29		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.16
MPC		0.64
ClinPred		0.48	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.067
gMVP		0.81

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3613218;