22-42871457-G-C

Variant names:

• chr22-42871457-G-C
• NM_001184970.3:c.1361C>G

Variant summary

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

The NM_001184970.3(PACSIN2):​c.1361C>G​(p.Thr454Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PACSIN2 NM_001184970.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.43
• Publications: 0 publications found

Genes affected

PACSIN2 (HGNC:8571): (protein kinase C and casein kinase substrate in neurons 2) This gene is a member of the protein kinase C and casein kinase substrate in neurons family. The encoded protein is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ENSG00000307798 (HGNC:):

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_001184970.3. 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
	PACSIN2	NM_001184970.3	MANE Select	c.1361C>G	p.Thr454Ser	missense	Exon 11 of 11	NP_001171899.1	Q9UNF0-1
	PACSIN2	NM_001349969.2		c.1367C>G	p.Thr456Ser	missense	Exon 12 of 12	NP_001336898.1
	PACSIN2	NM_001349970.2		c.1367C>G	p.Thr456Ser	missense	Exon 12 of 12	NP_001336899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACSIN2	ENST00000263246.8	TSL:1 MANE Select	c.1361C>G	p.Thr454Ser	missense	Exon 11 of 11	ENSP00000263246.3	Q9UNF0-1
	PACSIN2	ENST00000403744.7	TSL:1	c.1361C>G	p.Thr454Ser	missense	Exon 11 of 11	ENSP00000385372.3	Q9UNF0-1
	PACSIN2	ENST00000407585.5	TSL:1	c.1238C>G	p.Thr413Ser	missense	Exon 10 of 10	ENSP00000385952.1	Q9UNF0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Myoepithelial tumor (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.51	T
Sift4G	Benign	0.21	T
Polyphen		0.38	B
Vest4		0.55
MutPred		0.53		Gain of ubiquitination at K455 (P = 0.0961)
MVP		0.60
MPC		1.0
ClinPred		0.86	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.43
Mutation Taster		=66/34	polymorphism

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

hg19: chr22-43267463;