rs3762685

Variant names:

• chr3-146220832-T-C
• rs3762685
• NM_020353.3:c.101A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-146220832-T-C
• chr3-146220832-T-G

Variant summary

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

The NM_020353.3(PLSCR4):​c.101A>G​(p.Asn34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,598,748 control chromosomes in the GnomAD database, including 92,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9237 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83075 hom.)
• Consequence: PLSCR4 NM_020353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 32 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.427897E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR4	NM_020353.3	MANE Select	c.101A>G	p.Asn34Ser	missense	Exon 3 of 9	NP_065086.2
	PLSCR4	NM_001128304.2		c.101A>G	p.Asn34Ser	missense	Exon 5 of 11	NP_001121776.1
	PLSCR4	NM_001128305.2		c.101A>G	p.Asn34Ser	missense	Exon 3 of 9	NP_001121777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR4	ENST00000354952.7	TSL:1 MANE Select	c.101A>G	p.Asn34Ser	missense	Exon 3 of 9	ENSP00000347038.2
	PLSCR4	ENST00000446574.6	TSL:2	c.101A>G	p.Asn34Ser	missense	Exon 3 of 9	ENSP00000399315.2
	PLSCR4	ENST00000493382.5	TSL:2	c.101A>G	p.Asn34Ser	missense	Exon 5 of 11	ENSP00000419040.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52746 AN: 151908 Hom.: 9225 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.344 AC: 85739 AN: 249106 AF XY: 0.340

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.191

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.335 AC: 483953 AN: 1446724 Hom.: 83075 Cov.: 28 AF XY: 0.334 AC XY: 240402 AN XY: 720618

African (AFR) AF: 0.353 AC: 11696 AN: 33140

American (AMR) AF: 0.410 AC: 18125 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 11227 AN: 25990

East Asian (EAS) AF: 0.192 AC: 7584 AN: 39592

South Asian (SAS) AF: 0.298 AC: 25562 AN: 85684

European-Finnish (FIN) AF: 0.409 AC: 21820 AN: 53360

Middle Eastern (MID) AF: 0.245 AC: 1409 AN: 5750

European-Non Finnish (NFE) AF: 0.334 AC: 366587 AN: 1099056

Other (OTH) AF: 0.333 AC: 19943 AN: 59904

GnomAD4 genome AF: 0.347 AC: 52790 AN: 152024 Hom.: 9237 Cov.: 32 AF XY: 0.348 AC XY: 25891 AN XY: 74320

African (AFR) AF: 0.357 AC: 14781 AN: 41454

American (AMR) AF: 0.377 AC: 5758 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1336 AN: 4816

European-Finnish (FIN) AF: 0.410 AC: 4327 AN: 10550

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 23007 AN: 67968

Other (OTH) AF: 0.311 AC: 656 AN: 2112

Alfa AF: 0.339 Hom.: 39548

Bravo AF: 0.346

TwinsUK AF: 0.339 AC: 1256

ALSPAC AF: 0.340 AC: 1310

ESP6500AA AF: 0.350 AC: 1544

ESP6500EA AF: 0.351 AC: 3021

ExAC AF: 0.341 AC: 41369

Asia WGS AF: 0.232 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.071
DANN	Benign	0.72
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.00054	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L
PhyloP100		-2.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.049
Sift	Benign	0.40	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.072
MPC		0.060
ClinPred		0.015	T
GERP RS		-8.5
Varity_R		0.033
gMVP		0.12
Mutation Taster		=99/1	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: rs3762685; hg19: chr3-145938619; COSMIC: COSV61609201;