NM_020360.4:c.734G>T

Variant names:

• chr17-7390731-C-A
• rs764611196
• NM_020360.4:c.734G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020360.4(PLSCR3):​c.734G>T​(p.Arg245Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R245Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PLSCR3 NM_020360.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 0 publications found

Genes affected

PLSCR3 (HGNC:16495): (phospholipid scramblase 3) Enables several functions, including calcium-dependent protein binding activity; metal ion binding activity; and phospholipid scramblase activity. Involved in several processes, including cardiolipin biosynthetic process; regulation of apoptotic process; and regulation of release of cytochrome c from mitochondria. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM256-PLSCR3 (HGNC:49186): (TMEM256-PLSCR3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring chromosome 17 open reading frame 61 (C17orf61) and phospholipid scramblase 3 (PLSCR3) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020360.4. 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
	PLSCR3	NM_020360.4	MANE Select	c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	NP_065093.2
	PLSCR3	NM_001201576.2		c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	NP_001188505.1	Q9NRY6
	PLSCR3	NM_001369407.1		c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	NP_001356336.1	Q9NRY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR3	ENST00000619711.5	TSL:5 MANE Select	c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	ENSP00000483743.2	Q9NRY6
	PLSCR3	ENST00000324822.15	TSL:1	c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	ENSP00000316021.11	Q9NRY6
	PLSCR3	ENST00000574401.5	TSL:1	c.734G>T	p.Arg245Leu	missense	Exon 7 of 8	ENSP00000459019.1	Q9NRY6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727236

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.58	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.067
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.65	P
Vest4		0.63
MutPred		0.71		Loss of MoRF binding (P = 0.0284)
MVP		0.26
MPC		1.1
ClinPred		0.91	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.37
Mutation Taster		=77/23	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: rs764611196; hg19: chr17-7294050;