chr3-146449220-C-T

Variant names:

• chr3-146449220-C-T
• NM_001395437.1:c.631G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395437.1(PLSCR2):​c.631G>A​(p.Ala211Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLSCR2 NM_001395437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35430324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR2	NM_001395437.1	MANE Select	c.631G>A	p.Ala211Thr	missense	Exon 6 of 8	NP_001382366.1	Q9NRY7-1
	PLSCR2	NM_001199978.3		c.850G>A	p.Ala284Thr	missense	Exon 8 of 10	NP_001186907.1	Q9NRY7-2
	PLSCR2	NM_001395440.1		c.850G>A	p.Ala284Thr	missense	Exon 7 of 9	NP_001382369.1	Q9NRY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR2	ENST00000696113.1	MANE Select	c.631G>A	p.Ala211Thr	missense	Exon 6 of 8	ENSP00000512407.1	Q9NRY7-1
	PLSCR2	ENST00000613069.4	TSL:1	c.838G>A	p.Ala280Thr	missense	Exon 6 of 8	ENSP00000478902.1	Q9NRY7-3
	PLSCR2	ENST00000336685.6	TSL:1	c.631G>A	p.Ala211Thr	missense	Exon 7 of 9	ENSP00000338707.2	Q9NRY7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.0019
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.1
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.019	D
Vest4		0.33
MVP		0.43
MPC		0.66
ClinPred		0.93	D
GERP RS		1.4
Varity_R		0.15
gMVP		0.24
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr3-146167007;