3-146459990-C-T

Variant names:

• chr3-146459990-C-T
• rs571600120
• ENST00000613069.4:c.122G>A

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.134G>A​(p.Arg45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,460,904 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R45L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PLSCR2 NM_001199978.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• 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=0.07361156).

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.-86G>A		5_prime_UTR	Exon 2 of 8	NP_001382366.1	Q9NRY7-1
	PLSCR2	NM_001199978.3		c.134G>A	p.Arg45His	missense	Exon 4 of 10	NP_001186907.1	Q9NRY7-2
	PLSCR2	NM_001395440.1		c.134G>A	p.Arg45His	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.122G>A	p.Arg41His	missense	Exon 2 of 8	ENSP00000478902.1	Q9NRY7-3
	PLSCR2	ENST00000696113.1	MANE Select	c.-86G>A		5_prime_UTR	Exon 2 of 8	ENSP00000512407.1	Q9NRY7-1
	PLSCR2	ENST00000336685.6	TSL:1	c.-86G>A		5_prime_UTR	Exon 3 of 9	ENSP00000338707.2	Q9NRY7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248738 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460904 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726686

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000898 AC: 4 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111494

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.10
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.086
Sift	Benign	0.097	T
Sift4G	Benign	0.56	T
Vest4		0.034
MutPred		0.37		Gain of glycosylation at Y49 (P = 0.0015)
MVP		0.18
MPC		0.60
ClinPred		0.071	T
GERP RS		-1.7
PromoterAI		0.0073	Neutral
Varity_R		0.022
gMVP		0.10
Mutation Taster		=100/0	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: rs571600120; hg19: chr3-146177777;