chr3-146199890-C-T

Variant names:

• chr3-146199890-C-T
• rs1576448929
• NM_020353.3:c.547G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020353.3(PLSCR4):​c.547G>A​(p.Gly183Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: PLSCR4 NM_020353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19
• Publications: 0 publications found

Genes affected

PLSCR4 (HGNC:16497): (phospholipid scramblase 4) Enables CD4 receptor binding activity and enzyme binding activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to act upstream of or within cellular response to lipopolysaccharide. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020353.3. 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
	PLSCR4	NM_020353.3	MANE Select	c.547G>A	p.Gly183Ser	missense	Exon 6 of 9	NP_065086.2	Q9NRQ2-1
	PLSCR4	NM_001128304.2		c.547G>A	p.Gly183Ser	missense	Exon 8 of 11	NP_001121776.1	Q9NRQ2-1
	PLSCR4	NM_001128305.2		c.547G>A	p.Gly183Ser	missense	Exon 6 of 9	NP_001121777.1	Q9NRQ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR4	ENST00000354952.7	TSL:1 MANE Select	c.547G>A	p.Gly183Ser	missense	Exon 6 of 9	ENSP00000347038.2	Q9NRQ2-1
	PLSCR4	ENST00000446574.6	TSL:2	c.547G>A	p.Gly183Ser	missense	Exon 6 of 9	ENSP00000399315.2	Q9NRQ2-1
	PLSCR4	ENST00000493382.5	TSL:2	c.547G>A	p.Gly183Ser	missense	Exon 8 of 11	ENSP00000419040.1	Q9NRQ2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461384 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726980

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111774

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.23
BayesDel_addAF	Benign	0.0071	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.25
Sift	Benign	0.042	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.65		Gain of disorder (P = 0.05)
MVP		0.64
MPC		0.40
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.40
gMVP		0.53
Mutation Taster		=71/29	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: rs1576448929; hg19: chr3-145917677;