1-12777491-A-G

Position:

• chr1-12777491-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080830.5(PRAMEF12):​c.1344A>G​(p.Ile448Met) 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. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRAMEF12 NM_001080830.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.38

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04971999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF12	NM_001080830.5	c.1344A>G	p.Ile448Met	missense_variant	3/3	ENST00000357726.5	NP_001074299.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF12	ENST00000357726.5	c.1344A>G	p.Ile448Met	missense_variant	3/3	2	NM_001080830.5	ENSP00000350358	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0010
DEOGEN2	Benign	0.0011	T
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.050	T
PROVEAN	Benign	0.64	N
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Vest4		0.045
gMVP		0.20

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: rs848578; hg19: chr1-12837634;