rs189471842

Variant names:

• chr3-146521994-C-A
• rs189471842
• NM_021105.3:c.415G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-146521994-C-A
• chr3-146521994-C-T

Variant summary

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

The NM_021105.3(PLSCR1):​c.415G>T​(p.Val139Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V139I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PLSCR1 NM_021105.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 1 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.415G>T	p.Val139Phe	missense	Exon 6 of 9	NP_066928.1	O15162-1
	PLSCR1	NM_001406033.1		c.451G>T	p.Val151Phe	missense	Exon 7 of 10	NP_001392962.1
	PLSCR1	NM_001406034.1		c.415G>T	p.Val139Phe	missense	Exon 7 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.415G>T	p.Val139Phe	missense	Exon 6 of 9	ENSP00000345494.4	O15162-1
	PLSCR1	ENST00000493432.5	TSL:1	n.*11+3611G>T		intron	N/A	ENSP00000419680.1	F2Z3F2
	PLSCR1	ENST00000967305.1		c.415G>T	p.Val139Phe	missense	Exon 6 of 10	ENSP00000637364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251190 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461098 Hom.: 0 Cov.: 29 AF XY: 0.00000825 AC XY: 6 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111294

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.82
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.47		Loss of stability (P = 0.2633)
MVP		0.62
MPC		0.37
ClinPred		0.61	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.74
Mutation Taster		=59/41	polymorphism

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: rs189471842; hg19: chr3-146239781;