1-13223606-G-C

Variant names:

• chr1-13223606-G-C
• rs202229173
• NM_001099850.2:c.1166C>G

Variant summary

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

The NM_001099850.2(PRAMEF18):​c.1166C>G​(p.Thr389Arg) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T389M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32956636).

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.1166C>G	p.Thr389Arg	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.1166C>G	p.Thr389Arg	missense	Exon 3 of 3	ENSP00000485473.2	Q5VWM3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

Alfa AF: 0.000111 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0042	N
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.0
PrimateAI	Uncertain	0.64	T
MutPred		0.63		Gain of MoRF binding (P = 0.1109)
MVP		0.061
ClinPred		0.54	D
GERP RS		0.045
gMVP		0.58

Splicing

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

Other links and lift over

dbSNP: rs202229173; hg19: chr1-13329107;