1-12859779-T-C

Position:

• chr1-12859779-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_023014.1(PRAMEF2):​c.374T>C​(p.Phe125Ser) 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 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (576 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005810708).
• BP6: Variant 1-12859779-T-C is Benign according to our data. Variant chr1-12859779-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3025422.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF2	NM_023014.1	c.374T>C	p.Phe125Ser	missense_variant	3/4	ENST00000240189.2	NP_075390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.374T>C	p.Phe125Ser	missense_variant	3/4	1	NM_023014.1	ENSP00000240189	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1573 AN: 146660 Hom.: 12 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00255

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.00764

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0106

GnomAD3 exomes AF: 0.000628 AC: 155 AN: 246762 Hom.: 2 AF XY: 0.000637 AC XY: 85 AN XY: 133408

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.000889

Gnomad SAS exome AF: 0.00131

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000473

Gnomad OTH exome AF: 0.000998

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00201 AC: 2832 AN: 1412364 Hom.: 576 Cov.: 50 AF XY: 0.00220 AC XY: 1543 AN XY: 701544

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00209

Gnomad4 EAS exome AF: 0.00559

Gnomad4 SAS exome AF: 0.00683

Gnomad4 FIN exome AF: 0.000611

Gnomad4 NFE exome AF: 0.00158

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0107 AC: 1572 AN: 146760 Hom.: 12 Cov.: 32 AF XY: 0.0108 AC XY: 774 AN XY: 71618

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.00764

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0110

Alfa AF: 0.0147 Hom.: 13

ExAC AF: 0.00206 AC: 250

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	0.068
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.038
DANN	Benign	0.26
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00010	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.5	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.046
Sift	Benign	0.48	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.043
MVP		0.014
MPC		0.063
ClinPred		0.021	T
GERP RS		-0.15
Varity_R		0.033
gMVP		0.16

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: rs140362402; hg19: chr1-12919634; COSMIC: COSV53578712;