3-146455297-A-G

Position:

• chr3-146455297-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395437.1(PLSCR2):​c.263T>C​(p.Ile88Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLSCR2 NM_001395437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

Genes affected

PLSCR2 (HGNC:16494): (phospholipid scramblase 2) This gene encodes a member of the phospholipid scramblase family. Phospholipid scramblases are membrane proteins that mediate calcium-dependent, non-specific movement of plasma membrane phospholipids and phosphatidylserine exposure. The encoded protein contains a low affinity calcium binding motif and may play a role in blood coagulation and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

PLSCR2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR2	NM_001395437.1	c.263T>C	p.Ile88Thr	missense_variant	4/8	ENST00000696113.1	NP_001382366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR2	ENST00000696113.1	c.263T>C	p.Ile88Thr	missense_variant	4/8		NM_001395437.1	ENSP00000512407.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

The c.482T>C (p.I161T) alteration is located in exon 6 (coding exon 4) of the PLSCR2 gene. This alteration results from a T to C substitution at nucleotide position 482, causing the isoleucine (I) at amino acid position 161 to be replaced by a threonine (T). 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	0.80
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.1	.;.;M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.2	D;.;D;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;.;D;.;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Vest4		0.88
MVP		0.57
MPC		0.83
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.51
gMVP		0.58

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

Other links and lift over

dbSNP: rs2041144637; hg19: chr3-146173084;