chr1-54216247-G-C

Variant names:

• chr1-54216247-G-C
• rs13571
• NM_016491.4:c.1097G>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 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 (MetaRNN=1.4219017E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 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.1097G>C	p.Cys366Ser	missense	Exon 6 of 7	NP_057575.2
	MRPL37	NM_001330602.1		c.1097G>C	p.Cys366Ser	missense	Exon 6 of 7	NP_001317531.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL37	ENST00000360840.9	TSL:1 MANE Select	c.1097G>C	p.Cys366Ser	missense	Exon 6 of 7	ENSP00000354086.5
	MRPL37	ENST00000336230.10	TSL:1	c.704G>C	p.Cys235Ser	missense	Exon 4 of 5	ENSP00000338526.6
	MRPL37	ENST00000605337.5	TSL:5	c.1097G>C	p.Cys366Ser	missense	Exon 6 of 7	ENSP00000473980.1

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

GnomAD2 exomes AF: 0.677 AC: 170317 AN: 251460 AF XY: 0.676

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 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

African (AFR) AF: 0.645 AC: 21602 AN: 33476

American (AMR) AF: 0.621 AC: 27782 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 20484 AN: 26136

East Asian (EAS) AF: 0.431 AC: 17124 AN: 39700

South Asian (SAS) AF: 0.496 AC: 42755 AN: 86256

European-Finnish (FIN) AF: 0.708 AC: 37800 AN: 53420

Middle Eastern (MID) AF: 0.788 AC: 4542 AN: 5766

European-Non Finnish (NFE) AF: 0.774 AC: 860310 AN: 1111996

Other (OTH) AF: 0.723 AC: 43643 AN: 60396

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

African (AFR) AF: 0.646 AC: 26809 AN: 41498

American (AMR) AF: 0.666 AC: 10193 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2712 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2098 AN: 5164

South Asian (SAS) AF: 0.472 AC: 2276 AN: 4818

European-Finnish (FIN) AF: 0.700 AC: 7394 AN: 10568

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.772 AC: 52507 AN: 68004

Other (OTH) AF: 0.724 AC: 1524 AN: 2106

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 v4.9

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
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.9	N
PhyloP100		2.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.33		Gain of disorder (P = 2e-04)
MPC		0.34
ClinPred		0.0052	T
GERP RS		5.4
Varity_R		0.11
gMVP		0.11
Mutation Taster		=98/2	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: rs13571; hg19: chr1-54681920; COSMIC: COSV60321798;