Variant chr1-36462132-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_031280.4(MRPS15):c.207C>T(p.Pro69=) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.126

Variant links:

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]

MRPS15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MRPS15	NM_031280.4 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	3/8	ENST00000373116.6	NP_112570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS15	ENST00000373116.6 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	3/8	1	NM_031280.4	ENSP00000362208	P1
MRPS15	ENST00000462067.1 linkuse as main transcript	n.64+2150C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.953

AC:

144889

AN:

152080

Hom.:

69064

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.949

AC:

238285

AN:

251052

Hom.:

113227

AF XY:

0.948

AC XY:

128644

AN XY:

135694

show subpopulations

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 SAS exome

AF:

0.973

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.:

AF XY:

0.934

AC XY:

679109

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.977

Gnomad4 ASJ exome

AF:

0.974

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.973

Gnomad4 FIN exome

AF:

0.905

Gnomad4 NFE exome

AF:

0.924

Gnomad4 OTH exome

AF:

0.945

GnomAD4 genome

AF:

0.953

AC:

145000

AN:

152198

Hom.:

69117

Cov.:

AF XY:

0.953

AC XY:

70922

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.972

Gnomad4 ASJ

AF:

0.970

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.976

Gnomad4 FIN

AF:

0.905

Gnomad4 NFE

AF:

0.928

Gnomad4 OTH

AF:

0.963

Alfa

AF:

0.939

Hom.:

34985

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over