rs4613118

chr17-7394133-A-Gchr17-7394133-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020360.4(PLSCR3):c.-23T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,610,976 control chromosomes in the GnomAD database, including 530,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (39774 hom., cov: 30)
  • Exomes 𝑓: 0.81 (490269 hom.)
• Consequence: PLSCR3 NM_020360.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLSCR3	NM_020360.4	c.-23T>C		5_prime_UTR_variant	2/8	ENST00000619711.5
TMEM256-PLSCR3	NR_037719.1	n.482T>C		non_coding_transcript_exon_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLSCR3	ENST00000619711.5	c.-23T>C		5_prime_UTR_variant	2/8	5	NM_020360.4	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106546 AN: 151768 Hom.: 39770 Cov.: 30

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.724

GnomAD3 exomes AF: 0.707 AC: 173903 AN: 245826 Hom.: 66605 AF XY: 0.726 AC XY: 97056 AN XY: 133666

Gnomad AFR exome AF: 0.497

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.811

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.711

Gnomad FIN exome AF: 0.832

Gnomad NFE exome AF: 0.854

Gnomad OTH exome AF: 0.756

GnomAD4 exome AF: 0.809 AC: 1179949 AN: 1459090 Hom.: 490269 Cov.: 36 AF XY: 0.809 AC XY: 587073 AN XY: 725882

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.812

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.859

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.702 AC: 106597 AN: 151886 Hom.: 39774 Cov.: 30 AF XY: 0.694 AC XY: 51505 AN XY: 74238

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.718

Alfa AF: 0.816 Hom.: 49451

Bravo AF: 0.669

Asia WGS AF: 0.487 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	14
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4613118; hg19: chr17-7297452; COSMIC: COSV61169932; COSMIC: COSV61169932;