dbSNP rs3762685: PLSCR4:p.Asn34Ser (chr3-146220832-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020353.3(PLSCR4):c.101A>G(p.Asn34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,598,748 control chromosomes in the GnomAD database, including 92,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9237 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83075 hom. )

Consequence

PLSCR4
NM_020353.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.25

Publications

32 publications found

Variant links:

Genes affected

PLSCR4 (HGNC:16497): (phospholipid scramblase 4) Enables CD4 receptor binding activity and enzyme binding activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to act upstream of or within cellular response to lipopolysaccharide. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.427897E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLSCR4	NM_020353.3 link	c.101A>G	p.Asn34Ser	missense_variant	Exon 3 of 9	ENST00000354952.7	NP_065086.2	Q9NRQ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLSCR4	ENST00000354952.7 link	c.101A>G	p.Asn34Ser	missense_variant	Exon 3 of 9	1	NM_020353.3	ENSP00000347038.2		Q9NRQ2-1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52746

AN:

151908

Hom.:

9225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.314

GnomAD2 exomes

AF:

0.344

AC:

85739

AN:

249106

AF XY:

0.340

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.335

AC:

483953

AN:

1446724

Hom.:

83075

Cov.:

AF XY:

0.334

AC XY:

240402

AN XY:

720618

show subpopulations

African (AFR)

AF:

0.353

AC:

11696

AN:

33140

American (AMR)

AF:

0.410

AC:

18125

AN:

44248

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

11227

AN:

25990

East Asian (EAS)

AF:

0.192

AC:

7584

AN:

39592

South Asian (SAS)

AF:

0.298

AC:

25562

AN:

85684

European-Finnish (FIN)

AF:

0.409

AC:

21820

AN:

53360

Middle Eastern (MID)

AF:

0.245

AC:

1409

AN:

5750

European-Non Finnish (NFE)

AF:

0.334

AC:

366587

AN:

1099056

Other (OTH)

AF:

0.333

AC:

19943

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

13441

26882

40323

53764

67205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.347

AC:

52790

AN:

152024

Hom.:

9237

Cov.:

AF XY:

0.348

AC XY:

25891

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.357

AC:

14781

AN:

41454

American (AMR)

AF:

0.377

AC:

5758

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1519

AN:

3472

East Asian (EAS)

AF:

0.201

AC:

1038

AN:

5172

South Asian (SAS)

AF:

0.277

AC:

1336

AN:

4816

European-Finnish (FIN)

AF:

0.410

AC:

4327

AN:

10550

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

23007

AN:

67968

Other (OTH)

AF:

0.311

AC:

656

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1792

3583

5375

7166

8958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.339

Hom.:

39548

Bravo

AF:

0.346

TwinsUK

AF:

0.339

AC:

1256

ALSPAC

AF:

0.340

AC:

1310

ESP6500AA

AF:

0.350

AC:

1544

ESP6500EA

AF:

0.351

AC:

3021

ExAC

AF:

0.341

AC:

41369

Asia WGS

AF:

0.232

AC:

810

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.071

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0065

T;T;.;T;T;T;.;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.58

.;T;T;.;T;T;T;T;T;T

MetaRNN

Benign

0.00054

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.97

L;.;.;L;L;.;.;.;.;.

PhyloP100

-2.2

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.94

N;N;N;N;N;N;N;N;N;D

REVEL

Benign

0.049

Sift

Benign

0.40

T;D;T;T;T;T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T;T;.;T;.;.

Polyphen

0.0010

B;B;.;B;B;.;.;.;.;.

Vest4

0.072

MPC

0.060

ClinPred

0.015

GERP RS

-8.5

Varity_R

0.033

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs3762685

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over