1-12859091-A-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.82A>G(p.Met28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000089 (48 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.41

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=0.0049060285).
• BP6: Variant 1-12859091-A-G is Benign according to our data. Variant chr1-12859091-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.82A>G	p.Met28Val	missense_variant	2/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.82A>G	p.Met28Val	missense_variant	2/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147860 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00126 AC: 306 AN: 243594 Hom.: 26 AF XY: 0.00135 AC XY: 178 AN XY: 131646

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00149

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00267

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.000234

Gnomad NFE exome AF: 0.000975

Gnomad OTH exome AF: 0.00135

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000887 AC: 128 AN: 1443028 Hom.: 48 Cov.: 33 AF XY: 0.000102 AC XY: 73 AN XY: 718036

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000139

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.000260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000792

Gnomad4 OTH exome AF: 0.0000503

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147962 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72130

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00375 Hom.: 4

ExAC AF: 0.00313 AC: 379

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	0.067
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.015
Dann	Benign	0.31
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0014	N
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.46	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.084
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.017	D
Polyphen		0.0	B
Vest4		0.071
MVP		0.014
MPC		0.042
ClinPred		0.0027	T
GERP RS		-1.7
Varity_R		0.073
gMVP		0.37

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: rs138495825; hg19: chr1-12918946; COSMIC: COSV53577148;