Variant 6-34529413-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020804.5(PACSIN1):c.473A>G(p.Lys158Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Consequence

PACSIN1
NM_020804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.24

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:

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ACMG classification

Classification made for transcript

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
PACSIN1	NM_020804.5 linkuse as main transcript	c.473A>G	p.Lys158Arg	missense_variant	5/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.473A>G	p.Lys158Arg	missense_variant	5/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.473A>G	p.Lys158Arg	missense_variant	5/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.473A>G	p.Lys158Arg	missense_variant	5/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN1	ENST00000244458.7 linkuse as main transcript	c.473A>G	p.Lys158Arg	missense_variant	5/10	1	NM_020804.5	ENSP00000244458.2		Q9BY11

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Sep 30, 2024

The c.473A>G (p.K158R) alteration is located in exon 5 (coding exon 4) of the PACSIN1 gene. This alteration results from a A to G substitution at nucleotide position 473, causing the lysine (K) at amino acid position 158 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

.;D;.;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.6

M;.;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

.;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.026

.;D;D;D

Sift4G

Uncertain

0.056

T;T;T;T

Polyphen

0.98

D;.;D;D

Vest4

0.74

MutPred

0.25

Loss of glycosylation at K158 (P = 0.0448);.;Loss of glycosylation at K158 (P = 0.0448);Loss of glycosylation at K158 (P = 0.0448);

MVP

0.72

MPC

0.62

ClinPred

0.96

GERP RS

3.8

Varity_R

0.42

gMVP

0.31

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