3-146589673-T-C

Variant names:

• chr3-146589673-T-C
• rs201777851
• NM_001085420.2:c.757A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001085420.2(PLSCR5):​c.757A>G​(p.Ile253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,592,650 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PLSCR5 NM_001085420.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 4 publications found

Genes affected

PLSCR5 (HGNC:19952): (phospholipid scramblase family member 5) Predicted to enable phospholipid scramblase activity. Predicted to be involved in plasma membrane phospholipid scrambling. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLSCR5-AS1 (HGNC:40907): (PLSCR5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35193557).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085420.2. 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
	PLSCR5	NM_001085420.2	MANE Select	c.757A>G	p.Ile253Val	missense	Exon 6 of 8	NP_001078889.1	A0PG75-1
	PLSCR5	NM_001321245.2		c.721A>G	p.Ile241Val	missense	Exon 6 of 8	NP_001308174.1	A0PG75-2
	PLSCR5-AS1	NR_046698.1		n.72T>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR5	ENST00000443512.2	TSL:1 MANE Select	c.757A>G	p.Ile253Val	missense	Exon 6 of 8	ENSP00000390111.1	A0PG75-1
	PLSCR5	ENST00000482567.5	TSL:1	c.721A>G	p.Ile241Val	missense	Exon 6 of 8	ENSP00000418626.1	A0PG75-2
	PLSCR5	ENST00000492200.5	TSL:5	c.757A>G	p.Ile253Val	missense	Exon 6 of 8	ENSP00000417184.1	A0PG75-1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152112 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000124 AC: 30 AN: 241614 AF XY: 0.000114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000184

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000146 AC: 210 AN: 1440420 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 107 AN XY: 715866

African (AFR) AF: 0.0000607 AC: 2 AN: 32940

American (AMR) AF: 0.000185 AC: 8 AN: 43318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25528

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.0000360 AC: 3 AN: 83282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52738

Middle Eastern (MID) AF: 0.00265 AC: 15 AN: 5666

European-Non Finnish (NFE) AF: 0.000152 AC: 167 AN: 1098298

Other (OTH) AF: 0.000253 AC: 15 AN: 59370

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152230 Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74434

African (AFR) AF: 0.000120 AC: 5 AN: 41546

American (AMR) AF: 0.000588 AC: 9 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67970

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000230 Hom.: 2

Bravo AF: 0.000238

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.000149 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.94	P
Vest4		0.49
MVP		0.21
MPC		0.0021
ClinPred		0.21	T
GERP RS		5.4
Varity_R		0.38
gMVP		0.46
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs201777851; hg19: chr3-146307460;