22-42871457-G-C

Position:

• chr22-42871457-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

LOC101927393 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN2	NM_001184970.3	c.1361C>G	p.Thr454Ser	missense_variant	11/11	ENST00000263246.8	NP_001171899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN2	ENST00000263246.8	c.1361C>G	p.Thr454Ser	missense_variant	11/11	1	NM_001184970.3	ENSP00000263246.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Myoepithelial tumor Uncertain:1

Uncertain significance, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

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Computational scores

Source: dbNSFP v4.3

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;.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;.;.;.;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	.;L;.;L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.51	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.38	.;B;.;B;B
Vest4		0.55
MutPred		0.53		.;Gain of ubiquitination at K455 (P = 0.0961);.;Gain of ubiquitination at K455 (P = 0.0961);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-43267463;