rs777409763

Variant names:

• chr1-13223456-C-T
• rs777409763
• NM_001099850.2:c.1316G>A

Variant summary

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

The NM_001099850.2(PRAMEF18):​c.1316G>A​(p.Arg439His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 2)
  • Exomes 𝑓: 0.0000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.349
• Publications: 0 publications found

Genes affected

PRAMEF18 (HGNC:30693): (PRAME family member 18) 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19172901).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099850.2. 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
	PRAMEF18	NM_001099850.2	MANE Select	c.1316G>A	p.Arg439His	missense	Exon 3 of 3	NP_001093320.2	Q5VWM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF18	ENST00000624297.3	TSL:1 MANE Select	c.1316G>A	p.Arg439His	missense	Exon 3 of 3	ENSP00000485473.2	Q5VWM3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 26340 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000376 AC: 3 AN: 798558 Hom.: 0 Cov.: 13 AF XY: 0.00000488 AC XY: 2 AN XY: 409930

African (AFR) AF: 0.00 AC: 0 AN: 17806

American (AMR) AF: 0.00 AC: 0 AN: 24678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14334

East Asian (EAS) AF: 0.00 AC: 0 AN: 18886

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 63970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2450

European-Non Finnish (NFE) AF: 0.00000341 AC: 2 AN: 586260

Other (OTH) AF: 0.00 AC: 0 AN: 33340

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 26340 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 12174

African (AFR) AF: 0.00 AC: 0 AN: 4762

American (AMR) AF: 0.00 AC: 0 AN: 1698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 662

East Asian (EAS) AF: 0.00 AC: 0 AN: 944

South Asian (SAS) AF: 0.00 AC: 0 AN: 928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 15808

Other (OTH) AF: 0.00 AC: 0 AN: 350

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	0.099
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.00046	N
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.35
PrimateAI	Uncertain	0.58	T
MutPred		0.38		Loss of disorder (P = 0.0538)
MVP		0.014
ClinPred		0.85	D
GERP RS		-2.7
gMVP		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777409763; hg19: chr1-13328957;