1-12775685-C-A

Position:

• chr1-12775685-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080830.5(PRAMEF12):​c.430C>A​(p.Pro144Thr) 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: PRAMEF12 NM_001080830.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380

Genes affected

PRAMEF12 (HGNC:22125): (PRAME family member 12) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27261165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF12	NM_001080830.5	c.430C>A	p.Pro144Thr	missense_variant	2/3	ENST00000357726.5	NP_001074299.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF12	ENST00000357726.5	c.430C>A	p.Pro144Thr	missense_variant	2/3	2	NM_001080830.5	ENSP00000350358	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 29, 2023

The c.430C>A (p.P144T) alteration is located in exon 2 (coding exon 2) of the PRAMEF12 gene. This alteration results from a C to A substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Benign	0.022
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.44		Loss of glycosylation at P144 (P = 0.0455);
MVP		0.34
MPC		0.24
ClinPred		0.73	D
GERP RS		-0.29
Varity_R		0.027
gMVP		0.25

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: chr1-12835828;