chr1-13223433-G-T

Variant names:

• chr1-13223433-G-T
• rs1207603970
• NM_001099850.2:c.1339C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001099850.2(PRAMEF18):​c.1339C>A​(p.Pro447Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 2)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.741
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2	c.1339C>A	p.Pro447Thr	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.1339C>A	p.Pro447Thr	missense_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1223368 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 608456

African (AFR) AF: 0.00 AC: 0 AN: 27668

American (AMR) AF: 0.00 AC: 0 AN: 35954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19332

East Asian (EAS) AF: 0.00 AC: 0 AN: 21350

South Asian (SAS) AF: 0.00 AC: 0 AN: 78244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 950834

Other (OTH) AF: 0.00 AC: 0 AN: 47260

GnomAD4 genome Cov.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1339C>A (p.P447T) alteration is located in exon 3 (coding exon 3) of the PRAMEF18 gene. This alteration results from a C to A substitution at nucleotide position 1339, causing the proline (P) at amino acid position 447 to be replaced by a threonine (T). 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	0.36
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.0067	N
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.91	T
PhyloP100		-0.74
PrimateAI	Uncertain	0.53	T
MutPred		0.72		Loss of sheet (P = 0.0457);
MVP		0.048
ClinPred		0.73	D
GERP RS		0.36
gMVP		0.27

Splicing

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

Other links and lift over

dbSNP: rs1207603970; hg19: chr1-13328934;