1-12859755-C-G

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.350C>G(p.Pro117Arg) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P117S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (378 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0560

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=0.0074096024).
• BP6: Variant 1-12859755-C-G is Benign according to our data. Variant chr1-12859755-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025684.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.350C>G	p.Pro117Arg	missense_variant	3/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.350C>G	p.Pro117Arg	missense_variant	3/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1788 AN: 146850 Hom.: 22 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0283

Gnomad FIN AF: 0.00871

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0147

GnomAD3 exomes AF: 0.000649 AC: 160 AN: 246482 Hom.: 2 AF XY: 0.000607 AC XY: 81 AN XY: 133400

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.000502

Gnomad EAS exome AF: 0.00100

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000518

Gnomad OTH exome AF: 0.00100

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00157 AC: 2233 AN: 1421376 Hom.: 378 Cov.: 56 AF XY: 0.00179 AC XY: 1262 AN XY: 706074

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00485

Gnomad4 SAS exome AF: 0.00624

Gnomad4 FIN exome AF: 0.000687

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0122 AC: 1787 AN: 146948 Hom.: 22 Cov.: 32 AF XY: 0.0124 AC XY: 891 AN XY: 71706

Gnomad4 AFR AF: 0.00323

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0165

Gnomad4 SAS AF: 0.0281

Gnomad4 FIN AF: 0.00871

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0150

Alfa AF: 0.00895 Hom.: 5

ExAC AF: 0.00243 AC: 295

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: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	9.4
Dann	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0016	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.028
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.041	B
Vest4		0.11
MVP		0.13
MPC		0.055
ClinPred		0.0016	T
GERP RS		-0.29
Varity_R		0.038
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs559620534; hg19: chr1-12919610;