17-7392914-G-A

Position:

• chr17-7392914-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020360.4(PLSCR3):​c.546C>T​(p.His182His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,886 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (52 hom.)
• Consequence: PLSCR3 NM_020360.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.726

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]

PLSCR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001984626).
• BP6: Variant 17-7392914-G-A is Benign according to our data. Variant chr17-7392914-G-A is described in ClinVar as [Benign]. Clinvar id is 773062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.726 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR3	NM_020360.4	c.546C>T	p.His182His	synonymous_variant	6/8	ENST00000619711.5	NP_065093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR3	ENST00000619711.5	c.546C>T	p.His182His	synonymous_variant	6/8	5	NM_020360.4	ENSP00000483743.2
TMEM256-PLSCR3	ENST00000573331.5	n.*1344C>T		non_coding_transcript_exon_variant	9/11	2		ENSP00000466104.1
TMEM256-PLSCR3	ENST00000573331.5	n.*1344C>T		3_prime_UTR_variant	9/11	2		ENSP00000466104.1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2523 AN: 152154 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00419 AC: 1044 AN: 249190 Hom.: 25 AF XY: 0.00323 AC XY: 437 AN XY: 135182

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00172 AC: 2510 AN: 1461614 Hom.: 52 Cov.: 32 AF XY: 0.00149 AC XY: 1085 AN XY: 727122

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.0166 AC: 2524 AN: 152272 Hom.: 60 Cov.: 32 AF XY: 0.0159 AC XY: 1181 AN XY: 74456

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00686 Hom.: 16

Bravo AF: 0.0189

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0488 AC: 207

ESP6500EA AF: 0.000472 AC: 4

ExAC AF: 0.00505 AC: 611

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.55
DANN	Benign	0.84
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.19	N
MetaRNN	Benign	0.0020	T
MVP		0.15
ClinPred		0.0084	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs78000216; hg19: chr17-7296233;