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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2	c.1166C>G	p.Thr389Arg	missense_variant	Exon 3 of 3	ENST00000624297.3	NP_001093320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAMEF18	ENST00000624297.3	c.1166C>G	p.Thr389Arg	missense_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

Alfa AF: 0.000111 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1166C>G (p.T389R) alteration is located in exon 3 (coding exon 3) of the PRAMEF18 gene. This alteration results from a C to G substitution at nucleotide position 1166, causing the threonine (T) at amino acid position 389 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;