1-13223606-G-T

Variant names:

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

Variant summary

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

The NM_001099850.2(PRAMEF18):​c.1166C>A​(p.Thr389Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. T389M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.32968885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2	c.1166C>A	p.Thr389Lys	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>A	p.Thr389Lys	missense_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000359 AC: 1 AN: 278906 Hom.: 0 Cov.: 4 AF XY: 0.00000689 AC XY: 1 AN XY: 145196

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5522

American (AMR) AF: 0.00 AC: 0 AN: 9220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5668

East Asian (EAS) AF: 0.00 AC: 0 AN: 7870

South Asian (SAS) AF: 0.00 AC: 0 AN: 29952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1156

European-Non Finnish (NFE) AF: 0.00000519 AC: 1 AN: 192714

Other (OTH) AF: 0.00 AC: 0 AN: 12928

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0037	N
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.0
PrimateAI	Uncertain	0.65	T
MutPred		0.66		Gain of ubiquitination at T389 (P = 0.0177);
MVP		0.030
ClinPred		0.71	D
GERP RS		0.045
gMVP		0.55

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;