chr1-1402457-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017971.4(MRPL20):​c.277-201T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000928 in 1,185,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL20	NM_017971.4	c.277-201T>G		intron_variant	Intron 3 of 3	ENST00000344843.12	NP_060441.2
MRPL20	NM_001318485.2	c.*112T>G		3_prime_UTR_variant	Exon 4 of 4		NP_001305414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL20	ENST00000344843.12	c.277-201T>G		intron_variant	Intron 3 of 3	1	NM_017971.4	ENSP00000341082.7
MRPL20	ENST00000492508.1	c.*112T>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000459994.1
MRPL20	ENST00000487659.1	n.1350-201T>G		intron_variant	Intron 2 of 2	2
MRPL20	ENST00000493287.5	n.161-201T>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000928 AC: 11 AN: 1185974 Hom.: 0 Cov.: 30 AF XY: 0.00000527 AC XY: 3 AN XY: 569508

African (AFR) AF: 0.00 AC: 0 AN: 25874

American (AMR) AF: 0.00 AC: 0 AN: 12544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16762

East Asian (EAS) AF: 0.00 AC: 0 AN: 29442

South Asian (SAS) AF: 0.00 AC: 0 AN: 45722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3236

European-Non Finnish (NFE) AF: 0.0000112 AC: 11 AN: 978916

Other (OTH) AF: 0.00 AC: 0 AN: 48414

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: 5

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

Other links and lift over

dbSNP: rs1240709; hg19: chr1-1337837;