rs7065

Variant names:

• chr1-36462132-G-A
• rs7065
• NM_031280.4:c.207C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-36462132-G-A
• chr1-36462132-G-C
• chr1-36462132-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031280.4(MRPS15):​c.207C>T​(p.Pro69Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 1,612,898 control chromosomes in the GnomAD database, including 705,949 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 0.95 (69117 hom., cov: 31)
  • Exomes 𝑓: 0.93 (636832 hom.)
• Consequence: MRPS15 NM_031280.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

MRPS15 (HGNC:14504): (mitochondrial ribosomal protein S15) 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 S15P family. The encoded protein is more than two times the size of its E. coli counterpart, with the 12S rRNA binding sites conserved. Between human and mouse, the encoded protein is the least conserved among small subunit ribosomal proteins. Pseudogenes corresponding to this gene are found on chromosomes 15q and 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS15	NM_031280.4	c.207C>T	p.Pro69Pro	synonymous_variant	Exon 3 of 8	ENST00000373116.6	NP_112570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS15	ENST00000373116.6	c.207C>T	p.Pro69Pro	synonymous_variant	Exon 3 of 8	1	NM_031280.4	ENSP00000362208.5
MRPS15	ENST00000462067.1	n.64+2150C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144889 AN: 152080 Hom.: 69064 Cov.: 31

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.963

GnomAD2 exomes AF: 0.949 AC: 238285 AN: 251052 AF XY: 0.948

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.978

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.909

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.952

GnomAD4 exome AF: 0.933 AC: 1363514 AN: 1460700 Hom.: 636832 Cov.: 40 AF XY: 0.934 AC XY: 679109 AN XY: 726752

Gnomad4 AFR exome AF: 0.988 AC: 33048 AN: 33454

Gnomad4 AMR exome AF: 0.977 AC: 43651 AN: 44680

Gnomad4 ASJ exome AF: 0.974 AC: 25434 AN: 26106

Gnomad4 EAS exome AF: 1.00 AC: 39680 AN: 39686

Gnomad4 SAS exome AF: 0.973 AC: 83854 AN: 86190

Gnomad4 FIN exome AF: 0.905 AC: 48292 AN: 53368

Gnomad4 NFE exome AF: 0.924 AC: 1026891 AN: 1111114

Gnomad4 Remaining exome AF: 0.945 AC: 57036 AN: 60342

GnomAD4 genome AF: 0.953 AC: 145000 AN: 152198 Hom.: 69117 Cov.: 31 AF XY: 0.953 AC XY: 70922 AN XY: 74398

Gnomad4 AFR AF: 0.986 AC: 0.986053 AN: 0.986053

Gnomad4 AMR AF: 0.972 AC: 0.972291 AN: 0.972291

Gnomad4 ASJ AF: 0.970 AC: 0.970029 AN: 0.970029

Gnomad4 EAS AF: 0.999 AC: 0.99942 AN: 0.99942

Gnomad4 SAS AF: 0.976 AC: 0.975934 AN: 0.975934

Gnomad4 FIN AF: 0.905 AC: 0.905081 AN: 0.905081

Gnomad4 NFE AF: 0.928 AC: 0.928368 AN: 0.928368

Gnomad4 OTH AF: 0.963 AC: 0.963068 AN: 0.963068

Alfa AF: 0.945 Hom.: 51346

Bravo AF: 0.958

Asia WGS AF: 0.990 AC: 3440 AN: 3478

EpiCase AF: 0.933

EpiControl AF: 0.933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.9
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7065; hg19: chr1-36927733; COSMIC: COSV100118261; COSMIC: COSV100118261;