Variant 17-7393789-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020360.4(PLSCR3):c.55C>T(p.Pro19Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000258 in 1,513,344 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PLSCR3
NM_020360.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

PLSCR3 (HGNC:16495): (phospholipid scramblase 3) Enables several functions, including calcium-dependent protein binding activity; metal ion binding activity; and phospholipid scramblase activity. Involved in several processes, including cardiolipin biosynthetic process; regulation of apoptotic process; and regulation of release of cytochrome c from mitochondria. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR3 links:

TMEM256-PLSCR3 (HGNC:):

TMEM256-PLSCR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25935593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLSCR3	NM_020360.4 linkuse as main transcript	c.55C>T	p.Pro19Ser	missense_variant	3/8	ENST00000619711.5
TMEM256-PLSCR3	NR_037719.1 linkuse as main transcript	n.559C>T		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLSCR3	ENST00000619711.5 linkuse as main transcript	c.55C>T	p.Pro19Ser	missense_variant	3/8	5	NM_020360.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000264

AC:

AN:

113610

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

63092

show subpopulations

Gnomad AFR exome

AF:

0.000324

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:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1360984

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

672200

show subpopulations

Gnomad4 AFR exome

AF:

0.000405

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:

0.00000745

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000118

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0000653

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

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000162

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.55C>T (p.P19S) alteration is located in exon 3 (coding exon 2) of the PLSCR3 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a serine (S). 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

0.098

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

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

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.019

MetaRNN

Benign

0.26

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

N;N;.;N;N;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.8

D;D;.;.;.;.;.

REVEL

Benign

0.12

Sift

Benign

0.039

D;D;.;.;.;.;.

Sift4G

Benign

0.091

T;T;D;T;T;D;.

Polyphen

1.0

D;D;.;D;D;.;.

Vest4

0.54

MutPred

0.28

Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);Loss of catalytic residue at P19 (P = 0.0135);

MVP

0.60

MPC

0.54

ClinPred

0.39

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.14

gMVP

0.16

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