Genetic Variant PLSCR5:p.Glu211Gln (chr3-146589799-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001085420.2(PLSCR5):c.631G>C(p.Glu211Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000667 in 1,543,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

PLSCR5
NM_001085420.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

Variant links:

Genes affected

PLSCR5 (HGNC:19952): (phospholipid scramblase family member 5) Predicted to enable phospholipid scramblase activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR5 links:

PLSCR5-AS1 (HGNC:40907): (PLSCR5 antisense RNA 1)

PLSCR5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3850345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLSCR5	NM_001085420.2 link	c.631G>C	p.Glu211Gln	missense_variant	Exon 6 of 8	ENST00000443512.2	NP_001078889.1	A0PG75-1
PLSCR5	NM_001321245.2 link	c.595G>C	p.Glu199Gln	missense_variant	Exon 6 of 8		NP_001308174.1	A0PG75-2
PLSCR5	XM_017006373.2 link	c.631G>C	p.Glu211Gln	missense_variant	Exon 6 of 6		XP_016861862.1
PLSCR5-AS1	NR_046698.1 link	n.187+11C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLSCR5	ENST00000443512.2 link	c.631G>C	p.Glu211Gln	missense_variant	Exon 6 of 8	1	NM_001085420.2	ENSP00000390111.1	A0PG75-1
PLSCR5	ENST00000482567.5 link	c.595G>C	p.Glu199Gln	missense_variant	Exon 6 of 8	1		ENSP00000418626.1	A0PG75-2
PLSCR5	ENST00000492200.5 link	c.631G>C	p.Glu211Gln	missense_variant	Exon 6 of 8	5		ENSP00000417184.1	A0PG75-1
PLSCR5-AS1	ENST00000473817.1 link	n.187+11C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

229838

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

124932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.0000690

AC:

AN:

1391826

Hom.:

Cov.:

AF XY:

0.0000755

AC XY:

AN XY:

689176

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:

0.0000789

Gnomad4 OTH exome

AF:

0.000211

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000505

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.631G>C (p.E211Q) alteration is located in exon 6 (coding exon 6) of the PLSCR5 gene. This alteration results from a G to C substitution at nucleotide position 631, causing the glutamic acid (E) at amino acid position 211 to be replaced by a glutamine (Q). 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

0.24

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

.;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.4

M;.;M

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;D;N

REVEL

Benign

0.26

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.53

MVP

0.16

MPC

0.0045

ClinPred

0.58

GERP RS

5.9

Varity_R

0.40

gMVP

0.58

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

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