rs376455756

Variant names:

• chr19-3612141-C-A
• NM_001080543.2:c.2059G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3612141-C-A
• chr19-3612141-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080543.2(CACTIN):​c.2059G>T​(p.Asp687Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CACTIN NM_001080543.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACTIN	NM_001080543.2	c.2059G>T	p.Asp687Tyr	missense_variant	Exon 10 of 10	ENST00000429344.7	NP_001074012.1
CACTIN	NM_021231.2	c.2059G>T	p.Asp687Tyr	missense_variant	Exon 10 of 11		NP_067054.1
CACTIN-AS1	NR_038865.1	n.605C>A		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7	c.2059G>T	p.Asp687Tyr	missense_variant	Exon 10 of 10	1	NM_001080543.2	ENSP00000415078.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461368 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726974

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;T;D;D
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	.;D;.;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Uncertain	2.3	M;.;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.1	D;.;D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.66
MutPred		0.67		Gain of catalytic residue at D687 (P = 0.0413);.;Gain of catalytic residue at D687 (P = 0.0413);Gain of catalytic residue at D687 (P = 0.0413);
MVP		0.62
MPC		2.8
ClinPred		0.97	D
GERP RS		2.0
Varity_R		0.81
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-3612139;