chr6-34532484-G-A

Position:

chr6-34532484-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_020804.5(PACSIN1):c.1289G>A(p.Ser430Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 1,570,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

PACSIN1
NM_020804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

PACSIN1 (HGNC:8570): (protein kinase C and casein kinase substrate in neurons 1) Enables phospholipid binding activity. Involved in plasma membrane tubulation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PACSIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity PACN1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.02351129).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PACSIN1	ENST00000244458.7 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10	1	NM_020804.5	ENSP00000244458.2	Q9BY11
PACSIN1	ENST00000538621.2 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10	1		ENSP00000439639.1	Q9BY11
PACSIN1	ENST00000620693.4 linkuse as main transcript	c.1289G>A	p.Ser430Asn	missense_variant	10/10	1		ENSP00000484060.1	Q9BY11
PACSIN1	ENST00000374043.6 linkuse as main transcript	c.1163G>A	p.Ser388Asn	missense_variant	10/10	1		ENSP00000363155.1	F6U236

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000390

AC:

AN:

179382

Hom.:

AF XY:

0.0000524

AC XY:

AN XY:

95380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000519

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000705

AC:

AN:

1417988

Hom.:

Cov.:

AF XY:

0.00000856

AC XY:

AN XY:

701130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000268

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000592

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.1289G>A (p.S430N) alteration is located in exon 10 (coding exon 9) of the PACSIN1 gene. This alteration results from a G to A substitution at nucleotide position 1289, causing the serine (S) at amino acid position 430 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.059

T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.84

.;T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.76

N;.;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.12

.;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.49

.;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;.;B;B

Vest4

0.085

MutPred

0.37

Loss of phosphorylation at S430 (P = 0.1189);.;Loss of phosphorylation at S430 (P = 0.1189);Loss of phosphorylation at S430 (P = 0.1189);

MVP

0.32

MPC

1.5

ClinPred

0.033

GERP RS

2.8

Varity_R

0.094

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over