Variant 3-146455454-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395437.1(PLSCR2):c.106T>C(p.Phe36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PLSCR2
NM_001395437.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.305

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:

PLSCR2 (HGNC:):

PLSCR2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04399675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR2	NM_001395437.1 linkuse as main transcript	c.106T>C	p.Phe36Leu	missense_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.106T>C	p.Phe36Leu	missense_variant	4/8		NM_001395437.1	ENSP00000512407.1		Q9NRY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714896

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:

9.20e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 02, 2024

The c.325T>C (p.F109L) alteration is located in exon 6 (coding exon 4) of the PLSCR2 gene. This alteration results from a T to C substitution at nucleotide position 325, causing the phenylalanine (F) at amino acid position 109 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

0.29

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.024

DANN

Benign

0.24

DEOGEN2

Benign

0.0039

.;.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.49

.;T;T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.044

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;.;N;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

1.4

N;.;N;.;N

REVEL

Benign

0.0070

Sift

Benign

0.51

T;.;T;.;T

Sift4G

Benign

0.54

T;T;T;T;T

Vest4

0.056

MVP

0.061

MPC

0.24

ClinPred

0.056

GERP RS

-3.1

Varity_R

0.023

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over