rs1063796

Variant names:

• chr1-12861477-T-C
• rs1063796
• NM_023014.1:c.1123T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023014.1(PRAMEF2):​c.1123T>C​(p.Cys375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,505,846 control chromosomes in the GnomAD database, including 56,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6694 hom., cov: 30)
  • Exomes 𝑓: 0.25 (49514 hom.)
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.717
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014611274).
• BP6: Variant 1-12861477-T-C is Benign according to our data. Variant chr1-12861477-T-C is described in ClinVar as Benign. ClinVar VariationId is 403340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023014.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF2	NM_023014.1	MANE Select	c.1123T>C	p.Cys375Arg	missense	Exon 4 of 4	NP_075390.1	O60811

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF2	ENST00000240189.2	TSL:1 MANE Select	c.1123T>C	p.Cys375Arg	missense	Exon 4 of 4	ENSP00000240189.2	O60811

Frequencies

GnomAD3 genomes AF: 0.288 AC: 39689 AN: 137696 Hom.: 6676 Cov.: 30

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.376 AC: 72960 AN: 194116 AF XY: 0.373

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.433

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.247 AC: 338303 AN: 1368044 Hom.: 49514 Cov.: 61 AF XY: 0.246 AC XY: 167212 AN XY: 680852

African (AFR) AF: 0.399 AC: 12986 AN: 32554

American (AMR) AF: 0.174 AC: 7350 AN: 42144

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5252 AN: 25352

East Asian (EAS) AF: 0.191 AC: 5590 AN: 29200

South Asian (SAS) AF: 0.197 AC: 15929 AN: 80756

European-Finnish (FIN) AF: 0.256 AC: 12928 AN: 50554

Middle Eastern (MID) AF: 0.290 AC: 1145 AN: 3942

European-Non Finnish (NFE) AF: 0.251 AC: 262590 AN: 1047328

Other (OTH) AF: 0.259 AC: 14533 AN: 56214

GnomAD4 genome AF: 0.288 AC: 39736 AN: 137802 Hom.: 6694 Cov.: 30 AF XY: 0.288 AC XY: 19381 AN XY: 67182

African (AFR) AF: 0.397 AC: 15452 AN: 38922

American (AMR) AF: 0.222 AC: 2925 AN: 13200

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 606 AN: 3294

East Asian (EAS) AF: 0.239 AC: 863 AN: 3614

South Asian (SAS) AF: 0.212 AC: 869 AN: 4094

European-Finnish (FIN) AF: 0.256 AC: 2416 AN: 9452

Middle Eastern (MID) AF: 0.306 AC: 82 AN: 268

European-Non Finnish (NFE) AF: 0.254 AC: 15804 AN: 62242

Other (OTH) AF: 0.285 AC: 539 AN: 1892

Alfa AF: 0.312 Hom.: 1144

ExAC AF: 0.379 AC: 45951

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.056
DANN	Benign	0.12
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00011	N
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.72
PrimateAI	Benign	0.42	T
PROVEAN	Benign	4.0	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.019
MPC		0.063
ClinPred		0.00030	T
GERP RS		0.82
Varity_R		0.052
gMVP		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1063796; hg19: chr1-12921332; COSMIC: COSV53571909;