1-13223750-C-T

Variant names:

• chr1-13223750-C-T
• rs370025179
• NM_001099850.2:c.1022G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099850.2(PRAMEF18):​c.1022G>A​(p.Arg341Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 1)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRAMEF18 NM_001099850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.45

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.079367936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF18	NM_001099850.2	c.1022G>A	p.Arg341Gln	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.1022G>A	p.Arg341Gln	missense_variant	Exon 3 of 3	1	NM_001099850.2	ENSP00000485473.2

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000427 AC: 1 AN: 234324 Hom.: 0 Cov.: 2 AF XY: 0.00000802 AC XY: 1 AN XY: 124638

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: 0.0000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 1

Alfa AF: 0.0000509 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1022G>A (p.R341Q) 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 1022, causing the arginine (R) at amino acid position 341 to be replaced by a glutamine (Q). 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	Benign	0.088
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.10
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00029	N
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.56	T
MutPred		0.60		Gain of ubiquitination at K346 (P = 0.0804);
MVP		0.014
ClinPred		0.16	T
GERP RS		-1.6
Varity_R		0.026
gMVP		0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs370025179; hg19: chr1-13329251;