Genetic Variant PLSCR5:p.Gly254Asp (chr3-146589669-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001085420.2(PLSCR5):c.761G>A(p.Gly254Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000153 in 1,435,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PLSCR5
NM_001085420.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085420.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR5	NM_001085420.2	MANE Select	c.761G>A	p.Gly254Asp	missense	Exon 6 of 8	NP_001078889.1	A0PG75-1
PLSCR5	NM_001321245.2		c.725G>A	p.Gly242Asp	missense	Exon 6 of 8	NP_001308174.1	A0PG75-2
PLSCR5-AS1	NR_046698.1		n.68C>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLSCR5	ENST00000443512.2	TSL:1 MANE Select	c.761G>A	p.Gly254Asp	missense	Exon 6 of 8	ENSP00000390111.1	A0PG75-1
PLSCR5	ENST00000482567.5	TSL:1	c.725G>A	p.Gly242Asp	missense	Exon 6 of 8	ENSP00000418626.1	A0PG75-2
PLSCR5	ENST00000492200.5	TSL:5	c.761G>A	p.Gly254Asp	missense	Exon 6 of 8	ENSP00000417184.1	A0PG75-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000418

AC:

AN:

239212

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1435786

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

713090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32826

American (AMR)

AF:

0.00

AC:

AN:

42874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25394

East Asian (EAS)

AF:

0.00

AC:

AN:

39172

South Asian (SAS)

AF:

0.00

AC:

AN:

82674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

1095412

Other (OTH)

AF:

0.00

AC:

AN:

59148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

Cov.:

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.094

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.011

MutationAssessor

Pathogenic

3.4

PhyloP100

5.9

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.99

MutPred

0.91

Gain of sheet (P = 0.0827)

MVP

0.61

MPC

0.0035

ClinPred

0.99

GERP RS

4.4

Varity_R

0.95

gMVP

0.94

Mutation Taster

=49/51

disease causing

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over