12-89753657-T-C

Variant names:

• chr12-89753657-T-C
• rs10858925
• ENST00000546688.1:n.745T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000546688.1(MRPL2P1):​n.745T>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.695 in 514,632 control chromosomes in the GnomAD database, including 126,004 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 0.67 (34281 hom., cov: 31)
  • Exomes 𝑓: 0.71 (91723 hom.)
• Consequence: MRPL2P1 ENST00000546688.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 7 publications found

Genes affected

MRPL2P1 (HGNC:29698): (mitochondrial ribosomal protein L2 pseudogene 1)

ATP2B1-AS1 (HGNC:27883): (ATP2B1 antisense RNA 1)

ENSG00000296746 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL2P1		n.89753657T>C		intragenic_variant
LOC107984543	XR_007063399.1	n.170+36294T>C		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL2P1	ENST00000546688.1	n.745T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ATP2B1-AS1	ENST00000651272.1	n.359+36294T>C		intron_variant	Intron 2 of 6
ENSG00000296746	ENST00000741520.1	n.176-15220A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101285 AN: 151878 Hom.: 34252 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.681

GnomAD4 exome AF: 0.706 AC: 256103 AN: 362636 Hom.: 91723 Cov.: 0 AF XY: 0.720 AC XY: 147202 AN XY: 204532

African (AFR) AF: 0.561 AC: 5689 AN: 10142

American (AMR) AF: 0.551 AC: 16890 AN: 30628

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 6941 AN: 9128

East Asian (EAS) AF: 0.798 AC: 12407 AN: 15554

South Asian (SAS) AF: 0.811 AC: 47762 AN: 58904

European-Finnish (FIN) AF: 0.593 AC: 16573 AN: 27944

Middle Eastern (MID) AF: 0.709 AC: 1838 AN: 2592

European-Non Finnish (NFE) AF: 0.712 AC: 135855 AN: 190818

Other (OTH) AF: 0.718 AC: 12148 AN: 16926

GnomAD4 genome AF: 0.667 AC: 101359 AN: 151996 Hom.: 34281 Cov.: 31 AF XY: 0.662 AC XY: 49208 AN XY: 74282

African (AFR) AF: 0.576 AC: 23849 AN: 41428

American (AMR) AF: 0.606 AC: 9263 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2603 AN: 3470

East Asian (EAS) AF: 0.813 AC: 4208 AN: 5176

South Asian (SAS) AF: 0.813 AC: 3922 AN: 4822

European-Finnish (FIN) AF: 0.588 AC: 6206 AN: 10548

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48939 AN: 67964

Other (OTH) AF: 0.685 AC: 1441 AN: 2104

Alfa AF: 0.697 Hom.: 88450

Bravo AF: 0.659

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.46
PhyloP100		5.2

Splicing

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

Other links and lift over

dbSNP: rs10858925; hg19: chr12-90147434; COSMIC: COSV72764368;