Variant chr6-34531665-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020804.5(PACSIN1):c.1103C>T(p.Pro368Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,856 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PACSIN1
NM_020804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.16233441).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PACSIN1	ENST00000244458.7 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10	1	NM_020804.5	ENSP00000244458.2	Q9BY11
PACSIN1	ENST00000538621.2 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10	1		ENSP00000439639.1	Q9BY11
PACSIN1	ENST00000620693.4 linkuse as main transcript	c.1103C>T	p.Pro368Leu	missense_variant	9/10	1		ENSP00000484060.1	Q9BY11
PACSIN1	ENST00000374043.6 linkuse as main transcript	c.977C>T	p.Pro326Leu	missense_variant	9/10	1		ENSP00000363155.1	F6U236

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

AF:

0.00000342

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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:

0.0000113

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 11, 2022

The c.1103C>T (p.P368L) alteration is located in exon 9 (coding exon 8) of the PACSIN1 gene. This alteration results from a C to T substitution at nucleotide position 1103, causing the proline (P) at amino acid position 368 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;T;T

Eigen

Benign

0.011

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.83

.;T;.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;M;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.9

.;D;D;D

REVEL

Benign

0.073

Sift

Uncertain

0.0030

.;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.049

B;.;B;B

Vest4

0.13

MutPred

0.26

Loss of glycosylation at S365 (P = 0.0826);.;Loss of glycosylation at S365 (P = 0.0826);Loss of glycosylation at S365 (P = 0.0826);

MVP

0.36

MPC

0.48

ClinPred

0.98

GERP RS

4.9

Varity_R

0.27

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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