Variant 3-146521649-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_021105.3(PLSCR1):c.633C>A(p.His211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PLSCR1
NM_021105.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0890

Variant links:

Genes affected

PLSCR1 (HGNC:9092): (phospholipid scramblase 1) This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

PLSCR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a mutagenesis_site 60% reduction in nuclease activity; when associated with A-12; A-53; A-111 and A-262. (size 0) in uniprot entity PLS1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLSCR1	NM_021105.3 linkuse as main transcript	c.633C>A	p.His211Gln	missense_variant	7/9	ENST00000342435.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLSCR1	ENST00000342435.9 linkuse as main transcript	c.633C>A	p.His211Gln	missense_variant	7/9	1	NM_021105.3	P2	O15162-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251142

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135724

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460550

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726670

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000487

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 27, 2022

The c.633C>A (p.H211Q) alteration is located in exon 7 (coding exon 6) of the PLSCR1 gene. This alteration results from a C to A substitution at nucleotide position 633, causing the histidine (H) 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

Pathogenic

0.90

BayesDel_addAF

Benign

-0.0096

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.;T;.;T

Eigen

Benign

0.061

Eigen_PC

Benign

0.0065

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.45

T;T;T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

2.9

M;.;.;.;.;.

MutationTaster

Benign

0.87

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.8

D;D;D;D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.018

D;D;T;D;D;D

Sift4G

Benign

0.067

T;T;T;.;.;.

Polyphen

0.99

D;.;.;.;.;.

Vest4

0.59

MutPred

0.74

Loss of glycosylation at P215 (P = 0.1067);.;.;.;.;Loss of glycosylation at P215 (P = 0.1067);

MVP

0.40

MPC

0.53

ClinPred

0.96

GERP RS

2.3

Varity_R

0.73

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