1-12941230-T-A

Variant names:

• chr1-12941230-T-A
• NM_001010889.2:c.623A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001010889.2(PRAMEF6):​c.623A>T​(p.Gln208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 4)
• Consequence: PRAMEF6 NM_001010889.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.652
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28225803).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010889.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF6	NM_001010889.2	MANE Select	c.623A>T	p.Gln208Leu	missense	Exon 3 of 4	NP_001010889.1	Q5VXH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF6	ENST00000376189.5	TSL:1 MANE Select	c.623A>T	p.Gln208Leu	missense	Exon 3 of 4	ENSP00000365360.1	Q5VXH4
	PRAMEF6	ENST00000415464.6	TSL:1	c.623A>T	p.Gln208Leu	missense	Exon 3 of 4	ENSP00000401281.2	Q5VXH4

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.0060	N
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.65
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.045
Sift	Benign	0.030	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.13
MutPred		0.58		Loss of catalytic residue at Q208 (P = 0.0084)
MVP		0.082
MPC		2.8
ClinPred		0.88	D
GERP RS		1.5
Varity_R		0.11
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr1-13001060;