1-12859030-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_023014.1(PRAMEF2):c.21G>C(p.Pro7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,590,252 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00020 (52 hom.)
• Consequence: PRAMEF2 NM_023014.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 1-12859030-G-C is Benign according to our data. Variant chr1-12859030-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.85 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.21G>C	p.Pro7=	synonymous_variant	2/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.21G>C	p.Pro7=	synonymous_variant	2/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes AF: 0.000684 AC: 101 AN: 147764 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.000666

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000317

Gnomad OTH AF: 0.000500

GnomAD3 exomes AF: 0.00437 AC: 1026 AN: 234516 Hom.: 51 AF XY: 0.00429 AC XY: 545 AN XY: 127148

Gnomad AFR exome AF: 0.00233

Gnomad AMR exome AF: 0.00622

Gnomad ASJ exome AF: 0.00166

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.00672

Gnomad FIN exome AF: 0.000421

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.00606

GnomAD4 exome AF: 0.000196 AC: 282 AN: 1442384 Hom.: 52 Cov.: 33 AF XY: 0.000219 AC XY: 157 AN XY: 717126

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.000377

Gnomad4 ASJ exome AF: 0.000350

Gnomad4 EAS exome AF: 0.000491

Gnomad4 SAS exome AF: 0.000644

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.000387

GnomAD4 genome AF: 0.000683 AC: 101 AN: 147868 Hom.: 3 Cov.: 31 AF XY: 0.000623 AC XY: 45 AN XY: 72200

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00147

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.00181

Gnomad4 SAS AF: 0.000666

Gnomad4 FIN AF: 0.000288

Gnomad4 NFE AF: 0.000317

Gnomad4 OTH AF: 0.000495

Alfa AF: 0.00849 Hom.: 9

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

May 01, 2022

PRAMEF2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.4
Dann	Benign	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: rs17404792; hg19: chr1-12918885;