chr17-47824323-T-C

Position:

chr17-47824323-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145255.4(MRPL10):c.668A>G(p.Gln223Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MRPL10
NM_145255.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Variant links:

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]

MRPL10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17227513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MRPL10	NM_145255.4 linkuse as main transcript	c.668A>G	p.Gln223Arg	missense_variant	5/5	ENST00000351111.7
MRPL10	NM_148887.3 linkuse as main transcript	c.698A>G	p.Gln233Arg	missense_variant	6/6
MRPL10	XM_024450575.2 linkuse as main transcript	c.698A>G	p.Gln233Arg	missense_variant	6/6
MRPL10	NR_037575.2 linkuse as main transcript	n.847A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL10	ENST00000351111.7 linkuse as main transcript	c.668A>G	p.Gln223Arg	missense_variant	5/5	1	NM_145255.4	P1	Q7Z7H8-1
MRPL10	ENST00000290208.11 linkuse as main transcript	c.698A>G	p.Gln233Arg	missense_variant	5/5	2			Q7Z7H8-2
MRPL10	ENST00000414011.1 linkuse as main transcript	c.698A>G	p.Gln233Arg	missense_variant	6/6	3			Q7Z7H8-2
MRPL10	ENST00000421763.5 linkuse as main transcript	c.*670A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251214

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.698A>G (p.Q233R) alteration is located in exon 6 (coding exon 5) of the MRPL10 gene. This alteration results from a A to G substitution at nucleotide position 698, causing the glutamine (Q) at amino acid position 233 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.69

T;.;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

2.9

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.061

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.25

MutPred

0.64

Gain of solvent accessibility (P = 0.0055);.;.;

MVP

0.58

MPC

0.14

ClinPred

0.30

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over