Variant 3-146455459-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395437.1(PLSCR2):c.101T>G(p.Val34Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,571,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

PLSCR2
NM_001395437.1 missense, splice_region

Scores

Splicing: ADA: 0.0003205

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

PLSCR2 (HGNC:16494): (phospholipid scramblase 2) This gene encodes a member of the phospholipid scramblase family. Phospholipid scramblases are membrane proteins that mediate calcium-dependent, non-specific movement of plasma membrane phospholipids and phosphatidylserine exposure. The encoded protein contains a low affinity calcium binding motif and may play a role in blood coagulation and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

PLSCR2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12248376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR2	NM_001395437.1 linkuse as main transcript	c.101T>G	p.Val34Gly	missense_variant, splice_region_variant	4/8	ENST00000696113.1	NP_001382366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR2	ENST00000696113.1 linkuse as main transcript	c.101T>G	p.Val34Gly	missense_variant, splice_region_variant	4/8		NM_001395437.1	ENSP00000512407	P1	Q9NRY7-1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000559

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000395

AC:

AN:

248006

Hom.:

AF XY:

0.000372

AC XY:

AN XY:

134362

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.000758

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:

0.000587

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000635

AC:

901

AN:

1419270

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

448

AN XY:

708992

show subpopulations

Gnomad4 AFR exome

AF:

0.000185

Gnomad4 AMR exome

AF:

0.000788

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:

0.000758

Gnomad4 OTH exome

AF:

0.000763

GnomAD4 genome

AF:

0.000361

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.000543

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000533

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 08, 2022

The c.320T>G (p.V107G) alteration is located in exon 6 (coding exon 4) of the PLSCR2 gene. This alteration results from a T to G substitution at nucleotide position 320, causing the valine (V) at amino acid position 107 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

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.043

.;.;T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

.;T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

.;.;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-4.2

D;.;D;.;D

REVEL

Benign

0.20

Sift

Benign

0.058

T;.;T;.;T

Sift4G

Benign

0.31

T;T;T;T;T

Vest4

0.38

MVP

0.51

MPC

0.78

ClinPred

0.14

GERP RS

1.8

Varity_R

0.19

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.098

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