19-3620754-C-T

Position:

• chr19-3620754-C-T

Variant summary

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

The NM_001080543.2(CACTIN):​c.691G>A​(p.Glu231Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CACTIN NM_001080543.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60

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

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=0.10083744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACTIN	NM_001080543.2	c.691G>A	p.Glu231Lys	missense_variant	3/10	ENST00000429344.7
CACTIN	NM_021231.2	c.691G>A	p.Glu231Lys	missense_variant	3/11
CACTIN	XM_011528160.3	c.691G>A	p.Glu231Lys	missense_variant	3/8
CACTIN	XM_011528161.3	c.691G>A	p.Glu231Lys	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACTIN	ENST00000429344.7	c.691G>A	p.Glu231Lys	missense_variant	3/10	1	NM_001080543.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461290 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726924

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0076	T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.77	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.37	N;N;.
REVEL	Benign	0.097
Sift	Benign	0.83	T;T;.
Sift4G	Benign	0.92	T;T;T
Polyphen		0.028	B;B;B
Vest4		0.31
MutPred		0.35		Gain of MoRF binding (P = 0.0018);Gain of MoRF binding (P = 0.0018);Gain of MoRF binding (P = 0.0018);
MVP		0.043
MPC		1.4
ClinPred		0.92	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2033206429; hg19: chr19-3620752;