rs1890566

Positions:

• chr1-54202605-A-G

Variant summary

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

The NM_016491.4(MRPL37):​c.346+2016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,812 control chromosomes in the GnomAD database, including 9,965 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 0.35 (9965 hom., cov: 31)
• Consequence: MRPL37 NM_016491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL37	NM_016491.4	c.346+2016A>G		intron_variant		ENST00000360840.9	NP_057575.2
MRPL37	NM_001330602.1	c.346+2016A>G		intron_variant			NP_001317531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL37	ENST00000360840.9	c.346+2016A>G		intron_variant		1	NM_016491.4	ENSP00000354086	P1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52684 AN: 151692 Hom.: 9966 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52696 AN: 151812 Hom.: 9965 Cov.: 31 AF XY: 0.345 AC XY: 25592 AN XY: 74198

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.420

Alfa AF: 0.388 Hom.: 1605

Bravo AF: 0.342

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.58

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: rs1890566; hg19: chr1-54668278;