rs1890566

Variant names:

• chr1-54202605-A-G
• rs1890566
• NM_016491.4:c.346+2016A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016491.4. 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
	MRPL37	NM_016491.4	MANE Select	c.346+2016A>G		intron	N/A	NP_057575.2
	MRPL37	NM_001330602.1		c.346+2016A>G		intron	N/A	NP_001317531.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL37	ENST00000360840.9	TSL:1 MANE Select	c.346+2016A>G		intron	N/A	ENSP00000354086.5
	MRPL37	ENST00000336230.10	TSL:1	c.255+2016A>G		intron	N/A	ENSP00000338526.6
	MRPL37	ENST00000605337.5	TSL:5	c.346+2016A>G		intron	N/A	ENSP00000473980.1

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

African (AFR) AF: 0.202 AC: 8368 AN: 41354

American (AMR) AF: 0.359 AC: 5480 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1303 AN: 5138

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3947 AN: 10520

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 28982 AN: 67944

Other (OTH) AF: 0.420 AC: 881 AN: 2096

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.74
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: rs1890566; hg19: chr1-54668278;