1-1402457-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017971.4(MRPL20):c.277-201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,337,312 control chromosomes in the GnomAD database, including 76,441 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 0.44 (21672 hom., cov: 32)
  • Exomes 𝑓: 0.24 (54769 hom.)
• Consequence: MRPL20 NM_017971.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

Genes affected

MRPL20 (HGNC:14478): (mitochondrial ribosomal protein L20) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. A pseudogene corresponding to this gene is found on chromosome 21q. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL20	NM_017971.4	c.277-201T>C		intron_variant		ENST00000344843.12
MRPL20	NM_001318485.2	c.*112T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL20	ENST00000344843.12	c.277-201T>C		intron_variant		1	NM_017971.4	P1
MRPL20	ENST00000492508.1	c.*112T>C		3_prime_UTR_variant	3/3	2
MRPL20	ENST00000487659.1	n.1350-201T>C		intron_variant, non_coding_transcript_variant		2
MRPL20	ENST00000493287.5	n.161-201T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66523 AN: 151816 Hom.: 21594 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.242 AC: 286592 AN: 1185378 Hom.: 54769 Cov.: 30 AF XY: 0.247 AC XY: 140518 AN XY: 569166

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.439 AC: 66673 AN: 151934 Hom.: 21672 Cov.: 32 AF XY: 0.452 AC XY: 33531 AN XY: 74262

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.418

Alfa AF: 0.380 Hom.: 2419

Bravo AF: 0.471

Asia WGS AF: 0.832 AC: 2889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.6
Dann	Benign	0.67

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: rs1240709; hg19: chr1-1337837;