Variant chr1-36456211-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_031280.4(MRPS15):c.612G>A(p.Val204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00608 in 1,611,376 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 42 hom. )

Consequence

MRPS15
NM_031280.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.655

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-36456211-C-T is Benign according to our data. Variant chr1-36456211-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638673.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.655 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS15	NM_031280.4 linkuse as main transcript	c.612G>A	p.Val204=	synonymous_variant	7/8	ENST00000373116.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MRPS15	ENST00000373116.6 linkuse as main transcript	c.612G>A	p.Val204=	synonymous_variant	7/8	1	NM_031280.4	P1
MRPS15	ENST00000462067.1 linkuse as main transcript	n.1436G>A		non_coding_transcript_exon_variant	3/4	2
MRPS15	ENST00000477040.1 linkuse as main transcript	n.356G>A		non_coding_transcript_exon_variant	1/2	2
MRPS15	ENST00000488606.5 linkuse as main transcript	n.1949G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00800

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00395

AC:

986

AN:

249308

Hom.:

AF XY:

0.00400

AC XY:

539

AN XY:

134736

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00714

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00629

AC:

9178

AN:

1459086

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

4472

AN XY:

725608

show subpopulations

Gnomad4 AFR exome

AF:

0.000959

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00247

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00761

Gnomad4 OTH exome

AF:

0.00474

GnomAD4 genome

AF:

0.00409

AC:

623

AN:

152290

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00800

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00637

Hom.:

Bravo

AF:

0.00405

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

MRPS15: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.8

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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