3-146450432-T-C

Position:

• chr3-146450432-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395437.1(PLSCR2):​c.484-1065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,114 control chromosomes in the GnomAD database, including 25,768 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25768 hom., cov: 33)
• Consequence: PLSCR2 NM_001395437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR2	NM_001395437.1	c.484-1065A>G		intron_variant		ENST00000696113.1	NP_001382366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR2	ENST00000696113.1	c.484-1065A>G		intron_variant			NM_001395437.1	ENSP00000512407	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87724 AN: 151996 Hom.: 25738 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87802 AN: 152114 Hom.: 25768 Cov.: 33 AF XY: 0.583 AC XY: 43335 AN XY: 74338

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.575

Alfa AF: 0.587 Hom.: 3279

Bravo AF: 0.579

Asia WGS AF: 0.656 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.68

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: rs1403645; hg19: chr3-146168219;