rs151030123

Variant names:

• chr3-146455349-G-A
• rs151030123
• NM_001395437.1:c.211C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-146455349-G-A
• chr3-146455349-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395437.1(PLSCR2):​c.211C>T​(p.Arg71Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,612,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: PLSCR2 NM_001395437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.70
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08664477).

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.211C>T	p.Arg71Trp	missense	Exon 4 of 8	NP_001382366.1	Q9NRY7-1
	PLSCR2	NM_001199978.3		c.430C>T	p.Arg144Trp	missense	Exon 6 of 10	NP_001186907.1	Q9NRY7-2
	PLSCR2	NM_001395440.1		c.430C>T	p.Arg144Trp	missense	Exon 5 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.211C>T	p.Arg71Trp	missense	Exon 4 of 8	ENSP00000512407.1	Q9NRY7-1
	PLSCR2	ENST00000613069.4	TSL:1	c.418C>T	p.Arg140Trp	missense	Exon 4 of 8	ENSP00000478902.1	Q9NRY7-3
	PLSCR2	ENST00000336685.6	TSL:1	c.211C>T	p.Arg71Trp	missense	Exon 5 of 9	ENSP00000338707.2	Q9NRY7-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251358 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000959 AC: 140 AN: 1460584 Hom.: 0 Cov.: 30 AF XY: 0.0000936 AC XY: 68 AN XY: 726704

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1110872

Other (OTH) AF: 0.000149 AC: 9 AN: 60336

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74296

African (AFR) AF: 0.0000241 AC: 1 AN: 41412

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.000132

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	-0.42	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L
PhyloP100		-3.7
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0020	D
Vest4		0.14
MVP		0.14
MPC		0.47
ClinPred		0.16	T
GERP RS		-6.2
Varity_R		0.048
gMVP		0.28
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: rs151030123; hg19: chr3-146173136; COSMIC: COSV105208806;