rs756212569

Variant names:

• chr3-146460015-C-G
• rs756212569
• ENST00000613069.4:c.97G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199978.3(PLSCR2):​c.109G>C​(p.Gly37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PLSCR2 NM_001199978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0410
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12788638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199978.3. 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.-111G>C		5_prime_UTR	Exon 2 of 8	NP_001382366.1	Q9NRY7-1
	PLSCR2	NM_001199978.3		c.109G>C	p.Gly37Arg	missense	Exon 4 of 10	NP_001186907.1	Q9NRY7-2
	PLSCR2	NM_001395440.1		c.109G>C	p.Gly37Arg	missense	Exon 3 of 9	NP_001382369.1	Q9NRY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR2	ENST00000613069.4	TSL:1	c.97G>C	p.Gly33Arg	missense	Exon 2 of 8	ENSP00000478902.1	Q9NRY7-3
	PLSCR2	ENST00000696113.1	MANE Select	c.-111G>C		5_prime_UTR	Exon 2 of 8	ENSP00000512407.1	Q9NRY7-1
	PLSCR2	ENST00000336685.6	TSL:1	c.-111G>C		5_prime_UTR	Exon 3 of 9	ENSP00000338707.2	Q9NRY7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234414 AF XY: 0.00000788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000275 AC: 4 AN: 1455222 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723404

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.0000231 AC: 1 AN: 43374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 85744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108480

Other (OTH) AF: 0.00 AC: 0 AN: 60126

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.041
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.044
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.0090	D
Vest4		0.16
MutPred		0.44		Gain of glycosylation at Y42 (P = 0.0301)
MVP		0.22
MPC		0.24
ClinPred		0.16	T
GERP RS		-3.9
PromoterAI		0.0098	Neutral
Varity_R		0.064
gMVP		0.14
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs756212569; hg19: chr3-146177802;