chr12-89753487-C-T

Variant names:

• chr12-89753487-C-T
• rs882968
• ENST00000546688.1:n.575C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000546688.1(MRPL2P1):​n.575C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 557,158 control chromosomes in the GnomAD database, including 27 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 0.0093 (23 hom., cov: 31)
  • Exomes 𝑓: 0.00089 (4 hom.)
• Consequence: MRPL2P1 ENST00000546688.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 2 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=-0.56).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00934 (1420/152024) while in subpopulation AFR AF = 0.0327 (1353/41434). AF 95% confidence interval is 0.0312. There are 23 homozygotes in GnomAd4. There are 655 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL2P1		n.89753487C>T		intragenic_variant
LOC107984543	XR_007063399.1	n.170+36124C>T		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL2P1	ENST00000546688.1	n.575C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ATP2B1-AS1	ENST00000651272.1	n.359+36124C>T		intron_variant	Intron 2 of 6
ENSG00000296746	ENST00000741520.1	n.176-15050G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1413 AN: 151906 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.000891 AC: 361 AN: 405134 Hom.: 4 Cov.: 4 AF XY: 0.000699 AC XY: 154 AN XY: 220258

African (AFR) AF: 0.0270 AC: 279 AN: 10350

American (AMR) AF: 0.00162 AC: 39 AN: 24082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8058

East Asian (EAS) AF: 0.00 AC: 0 AN: 14738

South Asian (SAS) AF: 0.00 AC: 0 AN: 49454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32224

Middle Eastern (MID) AF: 0.00118 AC: 3 AN: 2534

European-Non Finnish (NFE) AF: 0.0000122 AC: 3 AN: 245202

Other (OTH) AF: 0.00200 AC: 37 AN: 18492

GnomAD4 genome AF: 0.00934 AC: 1420 AN: 152024 Hom.: 23 Cov.: 31 AF XY: 0.00882 AC XY: 655 AN XY: 74290

African (AFR) AF: 0.0327 AC: 1353 AN: 41434

American (AMR) AF: 0.00301 AC: 46 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67980

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00 Hom.: 1526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		3.4

Splicing

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

Other links and lift over

dbSNP: rs882968; hg19: chr12-90147264;