3-146525174-C-T

Variant names:

• chr3-146525174-C-T
• rs2587028
• NM_021105.3:c.355+431G>A

Variant summary

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

The NM_021105.3(PLSCR1):​c.355+431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,218 control chromosomes in the GnomAD database, including 1,109 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 0.11 (1109 hom., cov: 33)
• Consequence: PLSCR1 NM_021105.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021105.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR1	NM_021105.3	MANE Select	c.355+431G>A		intron	N/A	NP_066928.1
	PLSCR1	NM_001406033.1		c.391+431G>A		intron	N/A	NP_001392962.1
	PLSCR1	NM_001406034.1		c.355+431G>A		intron	N/A	NP_001392963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR1	ENST00000342435.9	TSL:1 MANE Select	c.355+431G>A		intron	N/A	ENSP00000345494.4
	PLSCR1	ENST00000493432.5	TSL:1	n.*11+431G>A		intron	N/A	ENSP00000419680.1
	PLSCR1	ENST00000487389.5	TSL:5	c.334+431G>A		intron	N/A	ENSP00000417792.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16955 AN: 152100 Hom.: 1109 Cov.: 33

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.111 AC: 16961 AN: 152218 Hom.: 1109 Cov.: 33 AF XY: 0.114 AC XY: 8453 AN XY: 74414

African (AFR) AF: 0.0489 AC: 2031 AN: 41552

American (AMR) AF: 0.154 AC: 2352 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 338 AN: 3468

East Asian (EAS) AF: 0.126 AC: 653 AN: 5174

South Asian (SAS) AF: 0.123 AC: 592 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8817 AN: 68004

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.124 Hom.: 2077

Bravo AF: 0.110

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.77
PhyloP100		-0.052
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: rs2587028; hg19: chr3-146242961;