Genetic Variant PLSCR1:p.Val139Ile (chr3-146521994-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_021105.3(PLSCR1):c.415G>A(p.Val139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PLSCR1
NM_021105.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.820

Publications

1 publications found

Variant links:

Genes affected

PLSCR1 (HGNC:9092): (phospholipid scramblase 1) This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

PLSCR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025799513).

BP6

Variant 3-146521994-C-T is Benign according to our data. Variant chr3-146521994-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2299449.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021105.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR1	NM_021105.3	MANE Select	c.415G>A	p.Val139Ile	missense	Exon 6 of 9	NP_066928.1	O15162-1
PLSCR1	NM_001406033.1		c.451G>A	p.Val151Ile	missense	Exon 7 of 10	NP_001392962.1
PLSCR1	NM_001406034.1		c.415G>A	p.Val139Ile	missense	Exon 7 of 10	NP_001392963.1	O15162-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR1	ENST00000342435.9	TSL:1 MANE Select	c.415G>A	p.Val139Ile	missense	Exon 6 of 9	ENSP00000345494.4	O15162-1
PLSCR1	ENST00000493432.5	TSL:1	n.*11+3611G>A		intron	N/A	ENSP00000419680.1	F2Z3F2
PLSCR1	ENST00000967305.1		c.415G>A	p.Val139Ile	missense	Exon 6 of 10	ENSP00000637364.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

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

GnomAD2 exomes

AF:

0.000107

AC:

AN:

251190

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461098

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000554

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111294

Other (OTH)

AF:

0.0000497

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.7

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.051

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.82

M_CAP

Benign

0.011

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

PhyloP100

0.82

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.27

REVEL

Benign

0.025

Sift

Benign

0.52

Sift4G

Benign

0.51

Polyphen

0.10

Vest4

0.10

MVP

0.20

MPC

0.13

ClinPred

0.029

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.21

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over