1-13223386-C-T

Variant names:

• chr1-13223386-C-T
• rs60378296
• NM_001099850.2:c.1386G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001099850.2(PRAMEF18):​c.1386G>A​(p.Thr462Thr) variant causes a synonymous 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 (★).

• Frequency:
  • Genomes: not found (cov: 3)
  • Exomes 𝑓: 0.000024 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.71

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2	c.1386G>A	p.Thr462Thr	synonymous_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.1386G>A	p.Thr462Thr	synonymous_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000243 AC: 30 AN: 1234922 Hom.: 8 Cov.: 28 AF XY: 0.0000293 AC XY: 18 AN XY: 614252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000302

Gnomad4 OTH exome AF: 0.0000209

GnomAD4 genome Cov.: 3

Alfa AF: 0.000168 Hom.: 456

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1386G>A (p.M462I) alteration is located in exon 3 (coding exon 3) of the PRAMEF18 gene. This alteration results from a G to A substitution at nucleotide position 1386, causing the methionine (M) at amino acid position 462 to be replaced by an isoleucine (I). 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
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60378296; hg19: chr1-13328887;