Variant 6-34531601-G-A 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.1039G>A(p.Val347Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

PACSIN1
NM_020804.5 missense, splice_region

Scores

Splicing: ADA: 0.9783

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

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:

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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.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10	ENST00000244458.7	NP_065855.1	Q9BY11Q5TZC3
PACSIN1	NM_001199583.3 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10		NP_001186512.1	Q9BY11Q5TZC3
PACSIN1	XM_011514541.2 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10		XP_011512843.1	Q9BY11Q5TZC3
PACSIN1	XM_047418689.1 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant, splice_region_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.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10	1	NM_020804.5	ENSP00000244458.2	Q9BY11
PACSIN1	ENST00000538621.2 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10	1		ENSP00000439639.1	Q9BY11
PACSIN1	ENST00000620693.4 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant, splice_region_variant	9/10	1		ENSP00000484060.1	Q9BY11
PACSIN1	ENST00000374043.6 linkuse as main transcript	c.913G>A	p.Val305Ile	missense_variant, splice_region_variant	9/10	1		ENSP00000363155.1	F6U236

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

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:

0.0000942

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:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

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:

0.0000942

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 18, 2023

The c.1039G>A (p.V347I) alteration is located in exon 9 (coding exon 8) of the PACSIN1 gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the valine (V) at amino acid position 347 to be replaced by an isoleucine (I). 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

0.099

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0020

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;T;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

L;.;L;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.46

.;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.15

.;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.016

B;.;B;B

Vest4

0.36

MutPred

0.20

Gain of glycosylation at S346 (P = 0.1064);.;Gain of glycosylation at S346 (P = 0.1064);Gain of glycosylation at S346 (P = 0.1064);

MVP

0.41

MPC

0.39

ClinPred

0.89

GERP RS

4.9

Varity_R

0.081

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.80

SpliceAI score (max)

0.030

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