3-146531132-T-C

Position:

• chr3-146531132-T-C

Variant summary

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

The ENST00000342435.9(PLSCR1):​c.95-2301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,040 control chromosomes in the GnomAD database, including 12,408 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 0.40 (12408 hom., cov: 32)
• Consequence: PLSCR1 ENST00000342435.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

PLSCR1 (HGNC:9092): (phospholipid scramblase 1) This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR1	NM_021105.3	c.95-2301A>G		intron_variant		ENST00000342435.9	NP_066928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR1	ENST00000342435.9	c.95-2301A>G		intron_variant		1	NM_021105.3	ENSP00000345494	P2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60882 AN: 151922 Hom.: 12379 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.401 AC: 60965 AN: 152040 Hom.: 12408 Cov.: 32 AF XY: 0.397 AC XY: 29501 AN XY: 74314

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.383

Alfa AF: 0.361 Hom.: 4420

Bravo AF: 0.408

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.77

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: rs2587025; hg19: chr3-146248919;