1-12859763-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_023014.1(PRAMEF2):c.358T>A(p.Trp120Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (430 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

Genes affected

PRAMEF2 (HGNC:28841): (PRAME family member 2) Predicted to be involved in several processes, including negative regulation of apoptotic process; negative regulation of transcription, DNA-templated; and positive regulation of cell population proliferation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0060358644).
• BP6: Variant 1-12859763-T-A is Benign according to our data. Variant chr1-12859763-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.358T>A	p.Trp120Arg	missense_variant	3/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.358T>A	p.Trp120Arg	missense_variant	3/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1671 AN: 146716 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.00841

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0147

GnomAD3 exomes AF: 0.000518 AC: 128 AN: 246876 Hom.: 1 AF XY: 0.000539 AC XY: 72 AN XY: 133548

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.000668

Gnomad SAS exome AF: 0.00104

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000410

Gnomad OTH exome AF: 0.000666

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00155 AC: 2195 AN: 1419320 Hom.: 430 Cov.: 58 AF XY: 0.00176 AC XY: 1238 AN XY: 705062

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.00169

Gnomad4 EAS exome AF: 0.00462

Gnomad4 SAS exome AF: 0.00591

Gnomad4 FIN exome AF: 0.000667

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0114 AC: 1669 AN: 146812 Hom.: 17 Cov.: 32 AF XY: 0.0116 AC XY: 834 AN XY: 71646

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.00841

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0146

Alfa AF: 0.0171 Hom.: 12

ExAC AF: 0.00241 AC: 292

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

PRAMEF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.039
Dann	Benign	0.20
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00041	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.052
Sift	Benign	0.82	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.45		Gain of loop (P = 0.0166);
MVP		0.076
MPC		0.063
ClinPred		0.020	T
GERP RS		-1.7
Varity_R		0.071
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs200248611; hg19: chr1-12919618; COSMIC: COSV105004894;