chr1-12777491-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001080830.5(PRAMEF12):​c.1344A>T​(p.Ile448Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,613,250 control chromosomes in the GnomAD database, including 33,725 homozygotes. 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 0.29 (8356 hom., cov: 32)
  • Exomes 𝑓: 0.20 (25369 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.15).
• BP7: Synonymous conserved (PhyloP=-5.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

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>T	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>T	p.Ile448Ile	synonymous	Exon 3 of 3	ENSP00000350358.4	O95522

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44626 AN: 151686 Hom.: 8319 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.201 AC: 293337 AN: 1461446 Hom.: 25369 Cov.: 34 AF XY: 0.200 AC XY: 145513 AN XY: 727008

African (AFR) AF: 0.581 AC: 19439 AN: 33476

American (AMR) AF: 0.165 AC: 7396 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3549 AN: 26134

East Asian (EAS) AF: 0.250 AC: 9921 AN: 39682

South Asian (SAS) AF: 0.224 AC: 19321 AN: 86234

European-Finnish (FIN) AF: 0.215 AC: 11496 AN: 53408

Middle Eastern (MID) AF: 0.208 AC: 1195 AN: 5758

European-Non Finnish (NFE) AF: 0.187 AC: 207818 AN: 1111666

Other (OTH) AF: 0.219 AC: 13202 AN: 60368

GnomAD4 genome AF: 0.295 AC: 44718 AN: 151804 Hom.: 8356 Cov.: 32 AF XY: 0.293 AC XY: 21764 AN XY: 74180

African (AFR) AF: 0.569 AC: 23551 AN: 41398

American (AMR) AF: 0.203 AC: 3103 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1306 AN: 5124

South Asian (SAS) AF: 0.221 AC: 1061 AN: 4804

European-Finnish (FIN) AF: 0.211 AC: 2226 AN: 10558

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12348 AN: 67880

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.187 Hom.: 1736

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.11
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs848578; hg19: chr1-12837634;