rs1047911

Variant names:

• chr2-74472651-C-A
• rs1047911
• NM_053050.5:c.10G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-74472651-C-A
• chr2-74472651-C-G
• chr2-74472651-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053050.5(MRPL53):​c.10G>T​(p.Ala4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,948 control chromosomes in the GnomAD database, including 55,147 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 0.34 (14160 hom., cov: 33)
  • Exomes 𝑓: 0.18 (40987 hom.)
• Consequence: MRPL53 NM_053050.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 46 publications found

Genes affected

MRPL53 (HGNC:16684): (mitochondrial ribosomal protein L53) 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. A pseudogene corresponding to this gene is found on chromosome 1p. [provided by RefSeq, Jul 2008]

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

ENSG00000286883 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0074633E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL53	NM_053050.5	c.10G>T	p.Ala4Ser	missense_variant	Exon 1 of 3	ENST00000258105.8	NP_444278.1
CCDC142	NM_001365575.2	c.*1895G>T		downstream_gene_variant		ENST00000393965.8	NP_001352504.1
CCDC142	NM_032779.4	c.*1895G>T		downstream_gene_variant			NP_116168.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL53	ENST00000258105.8	c.10G>T	p.Ala4Ser	missense_variant	Exon 1 of 3	1	NM_053050.5	ENSP00000258105.7
CCDC142	ENST00000393965.8	c.*1895G>T		downstream_gene_variant		1	NM_001365575.2	ENSP00000377537.3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51285 AN: 152078 Hom.: 14133 Cov.: 33

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.260 AC: 65408 AN: 251248 AF XY: 0.247

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.840

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.184 AC: 268306 AN: 1461752 Hom.: 40987 Cov.: 34 AF XY: 0.184 AC XY: 133492 AN XY: 727190

African (AFR) AF: 0.736 AC: 24650 AN: 33476

American (AMR) AF: 0.259 AC: 11568 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3295 AN: 26136

East Asian (EAS) AF: 0.833 AC: 33080 AN: 39698

South Asian (SAS) AF: 0.271 AC: 23375 AN: 86248

European-Finnish (FIN) AF: 0.140 AC: 7459 AN: 53418

Middle Eastern (MID) AF: 0.182 AC: 1048 AN: 5768

European-Non Finnish (NFE) AF: 0.135 AC: 150077 AN: 1111904

Other (OTH) AF: 0.228 AC: 13754 AN: 60384

GnomAD4 genome AF: 0.337 AC: 51366 AN: 152196 Hom.: 14160 Cov.: 33 AF XY: 0.337 AC XY: 25109 AN XY: 74414

African (AFR) AF: 0.717 AC: 29758 AN: 41500

American (AMR) AF: 0.266 AC: 4068 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3472

East Asian (EAS) AF: 0.824 AC: 4261 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1456 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9062 AN: 68000

Other (OTH) AF: 0.291 AC: 616 AN: 2114

Alfa AF: 0.212 Hom.: 15277

Bravo AF: 0.370

TwinsUK AF: 0.139 AC: 514

ALSPAC AF: 0.134 AC: 518

ESP6500AA AF: 0.706 AC: 3112

ESP6500EA AF: 0.138 AC: 1187

ExAC AF: 0.268 AC: 32521

Asia WGS AF: 0.566 AC: 1967 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.9
DANN	Benign	0.69
DEOGEN2	Benign	0.0055	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.54	T;T
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.21	N;.
PhyloP100		0.41
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.049
Sift	Benign	0.75	T;T
Sift4G	Benign	0.58	T;D
Polyphen		0.0	B;.
Vest4		0.10
MPC		0.42
ClinPred		0.0040	T
GERP RS		2.3
PromoterAI		0.074	Neutral
Varity_R		0.040
gMVP		0.19
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1047911; hg19: chr2-74699778; COSMIC: COSV50688557; COSMIC: COSV50688557;