chr1-12859771-G-T

Position:

• chr1-12859771-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_023014.1(PRAMEF2):​c.366G>T​(p.Leu122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (503 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF2 NM_023014.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.734

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 1-12859771-G-T is Benign according to our data. Variant chr1-12859771-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.734 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.366G>T	p.Leu122=	synonymous_variant	3/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.366G>T	p.Leu122=	synonymous_variant	3/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1624 AN: 146778 Hom.: 16 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00272

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0112

GnomAD3 exomes AF: 0.000669 AC: 165 AN: 246514 Hom.: 3 AF XY: 0.000683 AC XY: 91 AN XY: 133282

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.000891

Gnomad SAS exome AF: 0.00142

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000527

Gnomad OTH exome AF: 0.00100

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00167 AC: 2362 AN: 1417350 Hom.: 503 Cov.: 50 AF XY: 0.00185 AC XY: 1303 AN XY: 703952

Gnomad4 AFR exome AF: 0.000241

Gnomad4 AMR exome AF: 0.00294

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00496

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.000610

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0111 AC: 1623 AN: 146878 Hom.: 16 Cov.: 32 AF XY: 0.0113 AC XY: 807 AN XY: 71700

Gnomad4 AFR AF: 0.00271

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.0116

Alfa AF: 0.00723 Hom.: 4

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, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.46

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: rs771803377; hg19: chr1-12919626;