rs13571

chr1-54216247-G-Cchr1-54216247-G-T

Variant summary

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

The NM_016491.4(MRPL37):c.1097G>C(p.Cys366Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,613,990 control chromosomes in the GnomAD database, including 440,003 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.70 (37979 hom., cov: 32)
  • Exomes 𝑓: 0.74 (402024 hom.)
• Consequence: MRPL37 NM_016491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 (MetaRNN=1.4219017E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL37	NM_016491.4	c.1097G>C	p.Cys366Ser	missense_variant	6/7	ENST00000360840.9
MRPL37	NM_001330602.1	c.1097G>C	p.Cys366Ser	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL37	ENST00000360840.9	c.1097G>C	p.Cys366Ser	missense_variant	6/7	1	NM_016491.4	P1
MRPL37	ENST00000336230.10	c.704G>C	p.Cys235Ser	missense_variant	4/5	1
MRPL37	ENST00000605337.5	c.1097G>C	p.Cys366Ser	missense_variant	6/7	5
MRPL37	ENST00000398219.2	c.452G>C	p.Cys151Ser	missense_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106378 AN: 152004 Hom.: 37963 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.724

GnomAD3 exomes AF: 0.677 AC: 170317 AN: 251460 Hom.: 59674 AF XY: 0.676 AC XY: 91806 AN XY: 135900

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.494

Gnomad FIN exome AF: 0.704

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.719

GnomAD4 exome AF: 0.736 AC: 1076042 AN: 1461868 Hom.: 402024 Cov.: 70 AF XY: 0.729 AC XY: 530519 AN XY: 727238

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.621

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.774

Gnomad4 OTH exome AF: 0.723

GnomAD4 genome AF: 0.700 AC: 106436 AN: 152122 Hom.: 37979 Cov.: 32 AF XY: 0.690 AC XY: 51282 AN XY: 74352

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.724

Alfa AF: 0.745 Hom.: 10913

Bravo AF: 0.698

TwinsUK AF: 0.771 AC: 2858

ALSPAC AF: 0.780 AC: 3006

ESP6500AA AF: 0.657 AC: 2894

ESP6500EA AF: 0.783 AC: 6730

ExAC AF: 0.680 AC: 82593

Asia WGS AF: 0.484 AC: 1685 AN: 3478

EpiCase AF: 0.782

EpiControl AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	9.3
Dann	Benign	0.23
DEOGEN2	Benign	0.0023	T;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.23	T;T;T
MetaRNN	Benign	0.0000014	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	3.4	N;N;.
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.10
MutPred		0.33		.;Gain of disorder (P = 2e-04);Gain of disorder (P = 2e-04);
MPC		0.34
ClinPred		0.0052	T
GERP RS		5.4
Varity_R		0.11
gMVP		0.11

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: rs13571; hg19: chr1-54681920; COSMIC: COSV60321798;