Variant 6-34528824-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020804.5(PACSIN1):c.403G>T(p.Ala135Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PACSIN1
NM_020804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.99

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:

PACSIN1 (HGNC:):

PACSIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3429172).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5 linkuse as main transcript	c.403G>T	p.Ala135Ser	missense_variant	4/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.403G>T	p.Ala135Ser	missense_variant	4/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.403G>T	p.Ala135Ser	missense_variant	4/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.403G>T	p.Ala135Ser	missense_variant	4/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN1	ENST00000244458.7 linkuse as main transcript	c.403G>T	p.Ala135Ser	missense_variant	4/10	1	NM_020804.5	ENSP00000244458.2		Q9BY11

Frequencies

GnomAD3 genomes

AF:

0.0000791

AC:

AN:

151614

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251250

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1461388

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000220

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Feb 08, 2023

The c.403G>T (p.A135S) alteration is located in exon 4 (coding exon 3) of the PACSIN1 gene. This alteration results from a G to T substitution at nucleotide position 403, causing the alanine (A) at amino acid position 135 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;.;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

3.2

M;.;M;M

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

.;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.032

.;D;D;D

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.81

P;.;P;P

Vest4

0.60

MVP

0.59

MPC

1.1

ClinPred

0.39

GERP RS

4.0

Varity_R

0.69

gMVP

0.35

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