3-146440009-T-C

Variant names:

• chr3-146440009-T-C
• rs12489924
• NM_001395437.1:c.*34+1749A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395437.1(PLSCR2):​c.*34+1749A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,166 control chromosomes in the GnomAD database, including 4,024 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 0.22 (4024 hom., cov: 33)
• Consequence: PLSCR2 NM_001395437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLSCR2	NM_001395437.1	c.*34+1749A>G		intron_variant	Intron 7 of 7	ENST00000696113.1	NP_001382366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLSCR2	ENST00000696113.1	c.*34+1749A>G		intron_variant	Intron 7 of 7		NM_001395437.1	ENSP00000512407.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33356 AN: 152044 Hom.: 4022 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.219 AC: 33370 AN: 152166 Hom.: 4024 Cov.: 33 AF XY: 0.228 AC XY: 16924 AN XY: 74390

African (AFR) AF: 0.135 AC: 5624 AN: 41526

American (AMR) AF: 0.329 AC: 5029 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1515 AN: 5154

South Asian (SAS) AF: 0.256 AC: 1237 AN: 4826

European-Finnish (FIN) AF: 0.295 AC: 3124 AN: 10580

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15328 AN: 68002

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.215 Hom.: 512

Bravo AF: 0.218

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.18
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs12489924; hg19: chr3-146157796;