chr1-1402457-A-G

Variant names:

• chr1-1402457-A-G
• rs1240709
• NM_017971.4:c.277-201T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL20	NM_017971.4	MANE Select	c.277-201T>C		intron	N/A	NP_060441.2
	MRPL20	NM_001318485.2		c.*112T>C		3_prime_UTR	Exon 4 of 4	NP_001305414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL20	ENST00000344843.12	TSL:1 MANE Select	c.277-201T>C		intron	N/A	ENSP00000341082.7
	MRPL20	ENST00000492508.1	TSL:2	c.*112T>C		3_prime_UTR	Exon 3 of 3	ENSP00000459994.1
	MRPL20	ENST00000487659.1	TSL:2	n.1350-201T>C		intron	N/A

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

African (AFR) AF: 0.858 AC: 22190 AN: 25858

American (AMR) AF: 0.557 AC: 6969 AN: 12512

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 2897 AN: 16752

East Asian (EAS) AF: 0.989 AC: 29119 AN: 29442

South Asian (SAS) AF: 0.595 AC: 27165 AN: 45636

European-Finnish (FIN) AF: 0.257 AC: 6438 AN: 25010

Middle Eastern (MID) AF: 0.268 AC: 867 AN: 3232

European-Non Finnish (NFE) AF: 0.180 AC: 175697 AN: 978564

Other (OTH) AF: 0.315 AC: 15250 AN: 48372

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

African (AFR) AF: 0.830 AC: 34354 AN: 41410

American (AMR) AF: 0.510 AC: 7778 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 643 AN: 3462

East Asian (EAS) AF: 0.983 AC: 5076 AN: 5164

South Asian (SAS) AF: 0.628 AC: 3016 AN: 4806

European-Finnish (FIN) AF: 0.266 AC: 2808 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11881 AN: 67960

Other (OTH) AF: 0.418 AC: 883 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.67
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs1240709; hg19: chr1-1337837;