rs370025179

Variant names:

• chr1-13223750-C-T
• rs370025179
• NM_001099850.2:c.1022G>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.1022G>A​(p.Arg341Gln) 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: not found (cov: 1)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.45
• 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=0.079367936).

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.1022G>A	p.Arg341Gln	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.1022G>A	p.Arg341Gln	missense	Exon 3 of 3	ENSP00000485473.2	Q5VWM3

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000427 AC: 1 AN: 234324 Hom.: 0 Cov.: 2 AF XY: 0.00000802 AC XY: 1 AN XY: 124638

African (AFR) AF: 0.00 AC: 0 AN: 6630

American (AMR) AF: 0.00 AC: 0 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6484

East Asian (EAS) AF: 0.00 AC: 0 AN: 10650

South Asian (SAS) AF: 0.0000301 AC: 1 AN: 33190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 142054

Other (OTH) AF: 0.00 AC: 0 AN: 12926

GnomAD4 genome Cov.: 1

Alfa AF: 0.0000509 Hom.: 0

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	0.088
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.10
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00029	N
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.96	T
PhyloP100		-1.5
PrimateAI	Uncertain	0.56	T
MutPred		0.60		Gain of ubiquitination at K346 (P = 0.0804)
MVP		0.014
ClinPred		0.16	T
GERP RS		-1.6
gMVP		0.17

Splicing

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

Other links and lift over

dbSNP: rs370025179; hg19: chr1-13329251;