NM_001184970.3:c.1355A>G

Variant names:

• chr22-42871463-T-C
• rs1602154100
• NM_001184970.3:c.1355A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001184970.3(PACSIN2):​c.1355A>G​(p.Glu452Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PACSIN2 NM_001184970.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

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.1355A>G	p.Glu452Gly	missense	Exon 11 of 11	NP_001171899.1	Q9UNF0-1
	PACSIN2	NM_001349969.2		c.1361A>G	p.Glu454Gly	missense	Exon 12 of 12	NP_001336898.1
	PACSIN2	NM_001349970.2		c.1361A>G	p.Glu454Gly	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.1355A>G	p.Glu452Gly	missense	Exon 11 of 11	ENSP00000263246.3	Q9UNF0-1
	PACSIN2	ENST00000403744.7	TSL:1	c.1355A>G	p.Glu452Gly	missense	Exon 11 of 11	ENSP00000385372.3	Q9UNF0-1
	PACSIN2	ENST00000407585.5	TSL:1	c.1232A>G	p.Glu411Gly	missense	Exon 10 of 10	ENSP00000385952.1	Q9UNF0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460262 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726558

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110522

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.054	T
Polyphen		0.98	D
Vest4		0.84
MutPred		0.47		Loss of ubiquitination at K455 (P = 0.1016)
MVP		0.76
MPC		1.2
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.41
gMVP		0.78
Mutation Taster		=32/68	disease causing

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

dbSNP: rs1602154100; hg19: chr22-43267469;