6-42206740-A-G

Variant names:

• chr6-42206740-A-G
• rs4714579
• ENST00000718325.1:c.*1549T>C

Variant summary

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

The ENST00000718325.1(MRPS10):​c.*1549T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,112 control chromosomes in the GnomAD database, including 35,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35484 hom., cov: 32)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: MRPS10 ENST00000718325.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 17 publications found

Genes affected

MRPS10 (HGNC:14502): (mitochondrial ribosomal protein S10) 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 28S subunit protein that belongs to the ribosomal protein S10P family. Pseudogenes corresponding to this gene are found on chromosomes 1q, 3p, and 9p. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718325.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS10	NM_018141.4	MANE Select	c.*1549T>C		downstream_gene	N/A	NP_060611.2
	MRPS10	NM_001436638.1		c.*1549T>C		downstream_gene	N/A	NP_001423567.1	A0ABB0MVD6
	MRPS10	NM_001438206.1		c.*1549T>C		downstream_gene	N/A	NP_001425135.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS10	ENST00000718325.1		c.*1549T>C		3_prime_UTR	Exon 8 of 8	ENSP00000520760.1	A0ABB0MVD6
	MRPS10	ENST00000896501.1		c.*1549T>C		3_prime_UTR	Exon 7 of 7	ENSP00000566560.1
	MRPS10	ENST00000053468.4	TSL:1 MANE Select	c.*1549T>C		downstream_gene	N/A	ENSP00000053468.3	P82664

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102953 AN: 151988 Hom.: 35441 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.678 AC: 103053 AN: 152106 Hom.: 35484 Cov.: 32 AF XY: 0.684 AC XY: 50883 AN XY: 74348

African (AFR) AF: 0.564 AC: 23394 AN: 41482

American (AMR) AF: 0.730 AC: 11149 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2249 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4750 AN: 5180

South Asian (SAS) AF: 0.767 AC: 3694 AN: 4818

European-Finnish (FIN) AF: 0.783 AC: 8290 AN: 10586

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47264 AN: 67976

Other (OTH) AF: 0.681 AC: 1438 AN: 2112

Alfa AF: 0.689 Hom.: 52186

Bravo AF: 0.674

Asia WGS AF: 0.823 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.081
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4714579;

hg19: chr6-42174478;