1-12793928-C-G

Position:

• chr1-12793928-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023013.4(PRAMEF1):​c.301C>G​(p.Gln101Glu) 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. 12/21 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: PRAMEF1 NM_023013.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31

Genes affected

PRAMEF1 (HGNC:28840): (PRAME family member 1) This gene is a member of the PRAME (preferentially expressed antigen of melanoma) gene family which is expressed in many cancers but may function in reproductive tissues during development. Alternative promoter usage generates two transcript variants, which encode different isoforms. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22528994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF1	NM_023013.4	c.301C>G	p.Gln101Glu	missense_variant	3/4	ENST00000332296.7	NP_075389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF1	ENST00000332296.7	c.301C>G	p.Gln101Glu	missense_variant	3/4	1	NM_023013.4	ENSP00000332134	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Apr 05, 2023

The c.301C>G (p.Q101E) alteration is located in exon 3 (coding exon 2) of the PRAMEF1 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the glutamine (Q) at amino acid position 101 to be replaced by a glutamic acid (E). 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	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.057
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.018	D
Polyphen		0.82	P
Vest4		0.22
MutPred		0.58		Loss of MoRF binding (P = 0.0284);
MVP		0.076
MPC		0.51
ClinPred		0.58	D
GERP RS		0.71
Varity_R		0.041
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-12854077;