1-54200395-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000336230.10(MRPL37):c.61A>T(p.Arg21Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPL37 ENST00000336230.10 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

Genes affected

MRPL37 (HGNC:14034): (mitochondrial ribosomal protein L37) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000336230.10 Downstream stopcodon found after 348 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL37	NM_016491.4	c.152A>T	p.Glu51Val	missense_variant	1/7	ENST00000360840.9
MRPL37	NM_001330602.1	c.152A>T	p.Glu51Val	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL37	ENST00000360840.9	c.152A>T	p.Glu51Val	missense_variant	1/7	1	NM_016491.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 02, 2022

The c.152A>T (p.E51V) alteration is located in exon 1 (coding exon 1) of the MRPL37 gene. This alteration results from a A to T substitution at nucleotide position 152, causing the glutamic acid (E) at amino acid position 51 to be replaced by a valine (V). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.0050	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	A;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.99	D;.
Vest4		0.50
MutPred		0.57		Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);
MVP		0.37
MPC		0.96
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.61
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-54666068;