chr1-1405818-A-T

Position:

• chr1-1405818-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000344843.12(MRPL20):​c.267T>A​(p.Asn89Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPL20 ENST00000344843.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950

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]

MRPL20 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL20	NM_017971.4	c.267T>A	p.Asn89Lys	missense_variant	3/4	ENST00000344843.12	NP_060441.2
MRPL20	NM_001318485.2	c.267T>A	p.Asn89Lys	missense_variant	3/4		NP_001305414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL20	ENST00000344843.12	c.267T>A	p.Asn89Lys	missense_variant	3/4	1	NM_017971.4	ENSP00000341082.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.267T>A (p.N89K) alteration is located in exon 3 (coding exon 3) of the MRPL20 gene. This alteration results from a T to A substitution at nucleotide position 267, causing the asparagine (N) at amino acid position 89 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.24	T;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.020	D;.;.
Sift4G	Benign	0.19	T;D;D
Polyphen		0.46	P;.;.
Vest4		0.72
MutPred		0.65		Gain of methylation at N89 (P = 0.0191);.;Gain of methylation at N89 (P = 0.0191);
MVP		0.12
MPC		0.16
ClinPred		0.93	D
GERP RS		-5.7
Varity_R		0.84
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1341198;