1-12941386-T-A

Variant names:

• chr1-12941386-T-A
• NM_001010889.2:c.467A>T

Variant summary

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

The NM_001010889.2(PRAMEF6):​c.467A>T​(p.Lys156Met) 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: 9)
• Consequence: PRAMEF6 NM_001010889.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.15

Genes affected

PRAMEF6 (HGNC:30583): (PRAME family member 6) Enables ubiquitin ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21244231).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF6	NM_001010889.2	c.467A>T	p.Lys156Met	missense_variant	Exon 3 of 4	ENST00000376189.5	NP_001010889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAMEF6	ENST00000376189.5	c.467A>T	p.Lys156Met	missense_variant	Exon 3 of 4	1	NM_001010889.2	ENSP00000365360.1
PRAMEF6	ENST00000415464.6	c.467A>T	p.Lys156Met	missense_variant	Exon 3 of 4	1		ENSP00000401281.2

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.467A>T (p.K156M) alteration is located in exon 3 (coding exon 2) of the PRAMEF6 gene. This alteration results from a A to T substitution at nucleotide position 467, causing the lysine (K) at amino acid position 156 to be replaced by a methionine (M). 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	0.25
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0015	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.086
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.97	D;D
Vest4		0.15
MutPred		0.50		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.043
MPC		3.4
ClinPred		0.80	D
GERP RS		-3.0
Varity_R		0.16
gMVP		0.41

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: chr1-13001216;