NM_001010889.2:c.409G>T

Variant names:

• chr1-12941444-C-A
• rs758998491
• NM_001010889.2:c.409G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001010889.2(PRAMEF6):​c.409G>T​(p.Asp137Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D137H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF6 NM_001010889.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12411457).

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.409G>T	p.Asp137Tyr	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.409G>T	p.Asp137Tyr	missense	Exon 3 of 4	ENSP00000365360.1	Q5VXH4
	PRAMEF6	ENST00000415464.6	TSL:1	c.409G>T	p.Asp137Tyr	missense	Exon 3 of 4	ENSP00000401281.2	Q5VXH4

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1370322 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 682380

African (AFR) AF: 0.00 AC: 0 AN: 28512

American (AMR) AF: 0.00 AC: 0 AN: 41120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23802

East Asian (EAS) AF: 0.00 AC: 0 AN: 35888

South Asian (SAS) AF: 0.00 AC: 0 AN: 81906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050036

Other (OTH) AF: 0.00 AC: 0 AN: 55936

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.88
DEOGEN2	Benign	0.098	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0026	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-2.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.077
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.59	P
Vest4		0.11
MutPred		0.43		Loss of disorder (P = 0.0276)
MVP		0.043
MPC		2.6
ClinPred		0.56	D
GERP RS		-1.4
Varity_R		0.093
gMVP		0.30
Mutation Taster		=99/1	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

dbSNP: rs758998491; hg19: chr1-13001274;