Variant 6-34530259-C-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.805C>G(p.Arg269Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PACSIN1
NM_020804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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 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.805C>G	p.Arg269Gly	missense_variant	7/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PACSIN1	ENST00000244458.7 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10	1	NM_020804.5	ENSP00000244458.2	Q9BY11
PACSIN1	ENST00000538621.2 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10	1		ENSP00000439639.1	Q9BY11
PACSIN1	ENST00000620693.4 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	7/10	1		ENSP00000484060.1	Q9BY11
PACSIN1	ENST00000374043.6 linkuse as main transcript	c.679C>G	p.Arg227Gly	missense_variant	7/10	1		ENSP00000363155.1	F6U236

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250686

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

6.84e-7

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Jul 12, 2022

The c.805C>G (p.R269G) alteration is located in exon 7 (coding exon 6) of the PACSIN1 gene. This alteration results from a C to G substitution at nucleotide position 805, causing the arginine (R) at amino acid position 269 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;T;T;T

Eigen

Benign

0.019

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

.;D;.;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.;M;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.0

.;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.090

.;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.012

B;.;B;B

Vest4

0.77

MutPred

0.39

Loss of solvent accessibility (P = 0.0509);.;Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);

MVP

0.66

MPC

0.62

ClinPred

0.93

GERP RS

4.5

Varity_R

0.67

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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