1-12859825-G-T

Position:

• chr1-12859825-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023014.1(PRAMEF2):​c.420G>T​(p.Arg140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRAMEF2 NM_023014.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.251

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAMEF2	NM_023014.1	c.420G>T	p.Arg140Ser	missense_variant	3/4	ENST00000240189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAMEF2	ENST00000240189.2	c.420G>T	p.Arg140Ser	missense_variant	3/4	1	NM_023014.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.420G>T (p.R140S) alteration is located in exon 3 (coding exon 2) of the PRAMEF2 gene. This alteration results from a G to T substitution at nucleotide position 420, causing the arginine (R) at amino acid position 140 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.6
DANN	Benign	0.90
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0036	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.023
Sift	Benign	0.082	T
Sift4G	Benign	0.17	T
Polyphen		0.73	P
Vest4		0.20
MutPred		0.31		Gain of disorder (P = 0.0725);
MVP		0.092
MPC		0.28
ClinPred		0.55	D
GERP RS		-0.29
Varity_R		0.14
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-12919680;