3-146206579-G-A

Position:

• chr3-146206579-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020353.3(PLSCR4):​c.301C>T​(p.Pro101Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLSCR4 NM_020353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR4	NM_020353.3	c.301C>T	p.Pro101Ser	missense_variant	4/9	ENST00000354952.7	NP_065086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR4	ENST00000354952.7	c.301C>T	p.Pro101Ser	missense_variant	4/9	1	NM_020353.3	ENSP00000347038	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sensorineural hearing loss disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences

Sep 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.;T;T;T;.;.;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.62	.;T;T;.;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M;.;.;M;M;.;.;.;.
MutationTaster	Benign	0.86	D;D;D;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.4	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.13	T;T;T;T;T;T;D;T;T
Sift4G	Benign	0.063	T;T;T;T;T;T;.;T;.
Polyphen		0.98	D;P;.;D;D;.;.;.;.
Vest4		0.55
MutPred		0.48		Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);.;Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);Loss of glycosylation at P103 (P = 0.0087);
MVP		0.60
MPC		0.40
ClinPred		0.97	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-145924366;