chr3-146199893-T-C

Variant names:

• chr3-146199893-T-C
• rs751433522
• NM_020353.3:c.544A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020353.3(PLSCR4):​c.544A>G​(p.Met182Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: PLSCR4 NM_020353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.667
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034979522).

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.544A>G	p.Met182Val	missense	Exon 6 of 9	NP_065086.2	Q9NRQ2-1
	PLSCR4	NM_001128304.2		c.544A>G	p.Met182Val	missense	Exon 8 of 11	NP_001121776.1	Q9NRQ2-1
	PLSCR4	NM_001128305.2		c.544A>G	p.Met182Val	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.544A>G	p.Met182Val	missense	Exon 6 of 9	ENSP00000347038.2	Q9NRQ2-1
	PLSCR4	ENST00000446574.6	TSL:2	c.544A>G	p.Met182Val	missense	Exon 6 of 9	ENSP00000399315.2	Q9NRQ2-1
	PLSCR4	ENST00000493382.5	TSL:2	c.544A>G	p.Met182Val	missense	Exon 8 of 11	ENSP00000419040.1	Q9NRQ2-1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250988 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000807 AC: 118 AN: 1461392 Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000998 AC: 111 AN: 1111774

Other (OTH) AF: 0.0000994 AC: 6 AN: 60360

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.087
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.2
DANN	Benign	0.36
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.67
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Benign	0.52	T
Sift4G	Benign	0.57	T
Polyphen		0.17	B
Vest4		0.14
MutPred		0.35		Loss of catalytic residue at V178 (P = 0.0261)
MVP		0.13
MPC		0.075
ClinPred		0.034	T
GERP RS		-2.1
Varity_R		0.070
gMVP		0.30
Mutation Taster		=91/9	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: rs751433522; hg19: chr3-145917680;