17-7394133-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020360.4(PLSCR3):​c.-23T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460282 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111070

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 69428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.58
PhyloP100		1.2
PromoterAI		0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;