3-146528617-A-C

Variant names:

• chr3-146528617-A-C
• rs1343061898
• NM_021105.3:c.309T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021105.3(PLSCR1):​c.309T>G​(p.Ser103Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLSCR1 NM_021105.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.884
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR1	NM_021105.3	MANE Select	c.309T>G	p.Ser103Arg	missense	Exon 4 of 9	NP_066928.1	O15162-1
	PLSCR1	NM_001406033.1		c.345T>G	p.Ser115Arg	missense	Exon 5 of 10	NP_001392962.1
	PLSCR1	NM_001406034.1		c.309T>G	p.Ser103Arg	missense	Exon 5 of 10	NP_001392963.1	O15162-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR1	ENST00000342435.9	TSL:1 MANE Select	c.309T>G	p.Ser103Arg	missense	Exon 4 of 9	ENSP00000345494.4	O15162-1
	PLSCR1	ENST00000469266.1	TSL:1	n.583T>G		non_coding_transcript_exon	Exon 4 of 4
	PLSCR1	ENST00000493432.5	TSL:1	n.95-2970T>G		intron	N/A	ENSP00000419680.1	F2Z3F2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456744 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725000

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107326

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.88
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.048	D
Polyphen		0.12	B
Vest4		0.29
MutPred		0.35		Gain of catalytic residue at S103 (P = 0.0436)
MVP		0.35
MPC		0.19
ClinPred		0.84	D
GERP RS		1.8
PromoterAI		-0.0092	Neutral
Varity_R		0.25
gMVP		0.69
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1343061898; hg19: chr3-146246404;