Variant 3-146201064-T-C 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_020353.3(PLSCR4):c.368A>G(p.His123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,401,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

PLSCR4
NM_020353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

PLSCR4 (HGNC:16497): (phospholipid scramblase 4) Enables CD4 receptor binding activity and enzyme binding activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to act upstream of or within cellular response to lipopolysaccharide. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR4 links:

PLSCR4 (HGNC:):

PLSCR4 links:

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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=0.2584299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR4	NM_020353.3 linkuse as main transcript	c.368A>G	p.His123Arg	missense_variant	5/9	ENST00000354952.7	NP_065086.2	Q9NRQ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR4	ENST00000354952.7 linkuse as main transcript	c.368A>G	p.His123Arg	missense_variant	5/9	1	NM_020353.3	ENSP00000347038.2		Q9NRQ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000149

AC:

AN:

201124

Hom.:

AF XY:

0.00000910

AC XY:

AN XY:

109928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00000428

AC:

AN:

1401876

Hom.:

Cov.:

AF XY:

0.00000574

AC XY:

AN XY:

696378

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000195

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Nov 14, 2024

The c.368A>G (p.H123R) alteration is located in exon 5 (coding exon 4) of the PLSCR4 gene. This alteration results from a A to G substitution at nucleotide position 368, causing the histidine (H) at amino acid position 123 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0042

T;T;T;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.043

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.59

.;.;T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L;L;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D;D;.

Polyphen

0.064

B;B;B;.;.;.

Vest4

0.35

MutPred

0.64

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.24

MPC

0.10

ClinPred

0.27

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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