22-42876199-A-C

Variant names:

• chr22-42876199-A-C
• rs768766374
• NM_001184970.3:c.1286T>G

Variant summary

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

The NM_001184970.3(PACSIN2):​c.1286T>G​(p.Val429Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V429A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PACSIN2 NM_001184970.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.87
• 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]

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.1286T>G	p.Val429Gly	missense	Exon 10 of 11	NP_001171899.1	Q9UNF0-1
	PACSIN2	NM_001349969.2		c.1292T>G	p.Val431Gly	missense	Exon 11 of 12	NP_001336898.1
	PACSIN2	NM_001349970.2		c.1292T>G	p.Val431Gly	missense	Exon 11 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.1286T>G	p.Val429Gly	missense	Exon 10 of 11	ENSP00000263246.3	Q9UNF0-1
	PACSIN2	ENST00000403744.7	TSL:1	c.1286T>G	p.Val429Gly	missense	Exon 10 of 11	ENSP00000385372.3	Q9UNF0-1
	PACSIN2	ENST00000407585.5	TSL:1	c.1163T>G	p.Val388Gly	missense	Exon 9 of 10	ENSP00000385952.1	Q9UNF0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249560 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		8.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.67
MutPred		0.41		Loss of stability (P = 0.0274)
MVP		0.47
MPC		1.2
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.83
gMVP		0.84
Mutation Taster		=11/89	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: rs768766374; hg19: chr22-43272205;