chr1-12777491-A-C

Position:

• chr1-12777491-A-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.Ile448=) 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/exons	MANE	Protein	UniProt
PRAMEF12	NM_001080830.5	c.1344A>C	p.Ile448=	synonymous_variant	3/3	ENST00000357726.5	NP_001074299.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF12	ENST00000357726.5	c.1344A>C	p.Ile448=	synonymous_variant	3/3	2	NM_001080830.5	ENSP00000350358	P1

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;