19-3626924-T-G

Variant names:

• chr19-3626924-T-G
• rs2271875
• NM_001080543.2:c.-162A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080543.2(CACTIN):​c.-162A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 456,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CACTIN NM_001080543.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-162A>C		upstream_gene	N/A	NP_001074012.1	Q8WUQ7-1
	CACTIN	NM_021231.2		c.-162A>C		upstream_gene	N/A	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.-162A>C		upstream_gene	N/A	ENSP00000415078.1	Q8WUQ7-1
	CACTIN	ENST00000221899.7	TSL:1	c.-162A>C		upstream_gene	N/A	ENSP00000221899.4	Q8WUQ7-1
	CACTIN	ENST00000585942.5	TSL:1	n.-162A>C		upstream_gene	N/A	ENSP00000465751.1	Q8WUQ7-1

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000219 AC: 1 AN: 456800 Hom.: 0 AF XY: 0.00000435 AC XY: 1 AN XY: 229670

African (AFR) AF: 0.00 AC: 0 AN: 10298

American (AMR) AF: 0.00 AC: 0 AN: 7742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10802

East Asian (EAS) AF: 0.00 AC: 0 AN: 23696

South Asian (SAS) AF: 0.00 AC: 0 AN: 17958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 337278

Other (OTH) AF: 0.0000425 AC: 1 AN: 23510

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.44
PhyloP100		-0.21
PromoterAI		-0.017	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2271875;

hg19: chr19-3626922;