NM_001080830.5:c.1344A>C

Variant names:

• chr1-12777491-A-C
• rs848578
• NM_001080830.5:c.1344A>C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS1

The NM_001080830.5(PRAMEF12):​c.1344A>C​(p.Ile448Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,600,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (0 hom.)
• Consequence: PRAMEF12 NM_001080830.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.38

Genes affected

PRAMEF12 (HGNC:22125): (PRAME family member 12) 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 Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-5.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0141 (2140/151334) while in subpopulation SAS AF= 0.0335 (160/4772). AF 95% confidence interval is 0.0293. There are 0 homozygotes in gnomad4. There are 1108 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAMEF12	NM_001080830.5	c.1344A>C	p.Ile448Ile	synonymous_variant	Exon 3 of 3	ENST00000357726.5	NP_001074299.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAMEF12	ENST00000357726.5	c.1344A>C	p.Ile448Ile	synonymous_variant	Exon 3 of 3	2	NM_001080830.5	ENSP00000350358.4

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2142 AN: 151216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0179

GnomAD4 exome AF: 0.00313 AC: 4542 AN: 1448846 Hom.: 0 Cov.: 34 AF XY: 0.00354 AC XY: 2554 AN XY: 720698

Gnomad4 AFR exome AF: 0.000870

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.00692

Gnomad4 FIN exome AF: 0.00536

Gnomad4 NFE exome AF: 0.00241

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.0141 AC: 2140 AN: 151334 Hom.: 0 Cov.: 32 AF XY: 0.0150 AC XY: 1108 AN XY: 73958

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.0234

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0181

Alfa AF: 0.00143 Hom.: 1736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs848578; hg19: chr1-12837634;