NM_001080830.5:c.1344A>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

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
• Publications: 18 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Variant has high frequency in the EAS (0.0136) population. However there is too low homozygotes in high coverage region: (expected more than 6, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-5.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080830.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF12	NM_001080830.5	MANE Select	c.1344A>C	p.Ile448Ile	synonymous	Exon 3 of 3	NP_001074299.2	O95522

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAMEF12	ENST00000357726.5	TSL:2 MANE Select	c.1344A>C	p.Ile448Ile	synonymous	Exon 3 of 3	ENSP00000350358.4	O95522

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000870 AC: 29 AN: 33330

American (AMR) AF: 0.00220 AC: 98 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00192 AC: 50 AN: 26052

East Asian (EAS) AF: 0.0146 AC: 570 AN: 39074

South Asian (SAS) AF: 0.00692 AC: 589 AN: 85168

European-Finnish (FIN) AF: 0.00536 AC: 285 AN: 53186

Middle Eastern (MID) AF: 0.00422 AC: 24 AN: 5690

European-Non Finnish (NFE) AF: 0.00241 AC: 2655 AN: 1101910

Other (OTH) AF: 0.00404 AC: 242 AN: 59918

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00375 AC: 155 AN: 41342

American (AMR) AF: 0.0164 AC: 249 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3466

East Asian (EAS) AF: 0.0234 AC: 119 AN: 5086

South Asian (SAS) AF: 0.0335 AC: 160 AN: 4772

European-Finnish (FIN) AF: 0.0146 AC: 154 AN: 10542

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1218 AN: 67638

Other (OTH) AF: 0.0181 AC: 38 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00143 Hom.: 1736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs848578; hg19: chr1-12837634;