rs4613118

Variant names:

• chr17-7394133-A-G
• rs4613118
• NM_020360.4:c.-23T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7394133-A-G
• chr17-7394133-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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: Benign. The variant received -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.

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.-23T>C		5_prime_UTR	Exon 2 of 8	NP_065093.2
	PLSCR3	NM_001201576.2		c.-23T>C		5_prime_UTR	Exon 2 of 8	NP_001188505.1	Q9NRY6
	PLSCR3	NM_001369407.1		c.-23T>C		5_prime_UTR	Exon 2 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.-23T>C		5_prime_UTR	Exon 2 of 8	ENSP00000483743.2	Q9NRY6
	PLSCR3	ENST00000324822.15	TSL:1	c.-23T>C		5_prime_UTR	Exon 2 of 8	ENSP00000316021.11	Q9NRY6
	PLSCR3	ENST00000574401.5	TSL:1	c.-23T>C		5_prime_UTR	Exon 2 of 8	ENSP00000459019.1	Q9NRY6

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

GnomAD2 exomes AF: 0.707 AC: 173903 AN: 245826 AF XY: 0.726

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 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

African (AFR) AF: 0.503 AC: 16782 AN: 33396

American (AMR) AF: 0.442 AC: 19678 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 21187 AN: 26078

East Asian (EAS) AF: 0.291 AC: 11545 AN: 39636

South Asian (SAS) AF: 0.707 AC: 60768 AN: 85914

European-Finnish (FIN) AF: 0.839 AC: 44716 AN: 53300

Middle Eastern (MID) AF: 0.814 AC: 4672 AN: 5738

European-Non Finnish (NFE) AF: 0.859 AC: 953634 AN: 1110196

Other (OTH) AF: 0.779 AC: 46967 AN: 60270

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

African (AFR) AF: 0.506 AC: 20957 AN: 41384

American (AMR) AF: 0.576 AC: 8797 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2768 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1535 AN: 5116

South Asian (SAS) AF: 0.677 AC: 3252 AN: 4800

European-Finnish (FIN) AF: 0.826 AC: 8750 AN: 10594

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57959 AN: 67942

Other (OTH) AF: 0.718 AC: 1516 AN: 2110

Alfa AF: 0.789 Hom.: 69428

Bravo AF: 0.669

Asia WGS AF: 0.487 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	14
DANN	Benign	0.50
PhyloP100		1.2
PromoterAI		-0.029	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4613118; hg19: chr17-7297452; COSMIC: COSV61169932; COSMIC: COSV61169932;