3-146220832-T-C

Position:

• chr3-146220832-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

PLSCR4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR4	NM_020353.3	c.101A>G	p.Asn34Ser	missense_variant	3/9	ENST00000354952.7	NP_065086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR4	ENST00000354952.7	c.101A>G	p.Asn34Ser	missense_variant	3/9	1	NM_020353.3	ENSP00000347038.2

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

GnomAD3 exomes AF: 0.344 AC: 85739 AN: 249106 Hom.: 15220 AF XY: 0.340 AC XY: 45770 AN XY: 134682

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 SAS exome AF: 0.300

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

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.333

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

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.311

Alfa AF: 0.335 Hom.: 21566

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 v4.3

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;T;.;T;T;T;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.58	.;T;T;.;T;T;T;T;T;T
MetaRNN	Benign	0.00054	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L;.;.;L;L;.;.;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.94	N;N;N;N;N;N;N;N;N;D
REVEL	Benign	0.049
Sift	Benign	0.40	T;D;T;T;T;T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T;T;.;T;.;.
Polyphen		0.0010	B;B;.;B;B;.;.;.;.;.
Vest4		0.072
MPC		0.060
ClinPred		0.015	T
GERP RS		-8.5
Varity_R		0.033
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762685; hg19: chr3-145938619; COSMIC: COSV61609201;