17-47827054-C-T

Position:

• chr17-47827054-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145255.4(MRPL10):​c.373G>A​(p.Val125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,611,434 control chromosomes in the GnomAD database, including 102,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (6941 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95754 hom.)
• Consequence: MRPL10 NM_145255.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

Genes affected

MRPL10 (HGNC:14055): (mitochondrial ribosomal protein L10) 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. Sequence analysis identified three transcript variants that encode two different isoforms. A pseudogene corresponding to this gene is found on chromosome 5q. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020844042).
• BP6: Variant 17-47827054-C-T is Benign according to our data. Variant chr17-47827054-C-T is described in ClinVar as [Benign]. Clinvar id is 3059980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL10	NM_145255.4	c.373G>A	p.Val125Ile	missense_variant	3/5	ENST00000351111.7
MRPL10	NM_148887.3	c.403G>A	p.Val135Ile	missense_variant	4/6
MRPL10	XM_024450575.2	c.403G>A	p.Val135Ile	missense_variant	4/6
MRPL10	NR_037575.2	n.552G>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL10	ENST00000351111.7	c.373G>A	p.Val125Ile	missense_variant	3/5	1	NM_145255.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41240 AN: 152004 Hom.: 6939 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.266

GnomAD3 exomes AF: 0.286 AC: 71215 AN: 248826 Hom.: 12200 AF XY: 0.294 AC XY: 39528 AN XY: 134440

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.0127

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.351 AC: 511891 AN: 1459312 Hom.: 95754 Cov.: 39 AF XY: 0.348 AC XY: 252627 AN XY: 725866

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.0123

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.271 AC: 41259 AN: 152122 Hom.: 6941 Cov.: 32 AF XY: 0.269 AC XY: 20040 AN XY: 74372

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.264

Alfa AF: 0.348 Hom.: 15222

Bravo AF: 0.251

TwinsUK AF: 0.381 AC: 1412

ALSPAC AF: 0.390 AC: 1503

ESP6500AA AF: 0.112 AC: 493

ESP6500EA AF: 0.381 AC: 3273

ExAC AF: 0.287 AC: 34896

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MRPL10-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.8
DANN	Benign	0.84
DEOGEN2	Benign	0.036	T;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.55	T;.;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.35	N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.033
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.047
MPC		0.11
ClinPred		0.0022	T
GERP RS		-0.13
Varity_R		0.069
gMVP		0.55

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: rs11538868; hg19: chr17-45904420; COSMIC: COSV51621557; COSMIC: COSV51621557;