3-146589697-C-T

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001085420.2(PLSCR5):c.733G>A(p.Asp245Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,606,298 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PLSCR5
NM_001085420.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLSCR5	NM_001085420.2 link	c.733G>A	p.Asp245Asn	missense_variant	Exon 6 of 8	ENST00000443512.2	NP_001078889.1	A0PG75-1
PLSCR5	NM_001321245.2 link	c.697G>A	p.Asp233Asn	missense_variant	Exon 6 of 8		NP_001308174.1	A0PG75-2
PLSCR5	XM_017006373.2 link	c.733G>A	p.Asp245Asn	missense_variant	Exon 6 of 6		XP_016861862.1
PLSCR5-AS1	NR_046698.1 link	n.96C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLSCR5	ENST00000443512.2 link	c.733G>A	p.Asp245Asn	missense_variant	Exon 6 of 8	1	NM_001085420.2	ENSP00000390111.1	A0PG75-1
PLSCR5	ENST00000482567.5 link	c.697G>A	p.Asp233Asn	missense_variant	Exon 6 of 8	1		ENSP00000418626.1	A0PG75-2
PLSCR5	ENST00000492200.5 link	c.733G>A	p.Asp245Asn	missense_variant	Exon 6 of 8	5		ENSP00000417184.1	A0PG75-1
PLSCR5-AS1	ENST00000473817.1 link	n.96C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152142

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247262

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.0000885

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454156

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723470

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000674

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.733G>A (p.D245N) alteration is located in exon 6 (coding exon 6) of the PLSCR5 gene. This alteration results from a G to A substitution at nucleotide position 733, causing the aspartic acid (D) at amino acid position 245 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

-0.012

MutationAssessor

Pathogenic

3.1

M;.;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.025

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

0.96

D;.;D

Vest4

0.85

MutPred

0.84

Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);

MVP

0.40

MPC

0.0039

ClinPred

0.94

GERP RS

5.3

Varity_R

0.49

gMVP

0.63

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