1-175014705-A-G

Position:

• chr1-175014705-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000476371.1(MRPS14):​c.351T>C​(p.His117His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,613,342 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (79 hom.)
• Consequence: MRPS14 ENST00000476371.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.556

Genes affected

MRPS14 (HGNC:14049): (mitochondrial ribosomal protein S14) 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 S14P family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

MRPS14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-175014705-A-G is Benign according to our data. Variant chr1-175014705-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1176521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.556 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS14	NM_022100.3	c.351T>C	p.His117His	synonymous_variant	3/3	ENST00000476371.1	NP_071383.1
MRPS14	NR_037606.2	n.460T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS14	ENST00000476371.1	c.351T>C	p.His117His	synonymous_variant	3/3	1	NM_022100.3	ENSP00000420714.1
MRPS14	ENST00000367677.3	n.*260T>C		non_coding_transcript_exon_variant	3/3	1		ENSP00000431220.1
MRPS14	ENST00000367677.3	n.*260T>C		3_prime_UTR_variant	3/3	1		ENSP00000431220.1
MRPS14	ENST00000498253.1	n.120T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1069 AN: 152148 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00822

Gnomad OTH AF: 0.00624

GnomAD3 exomes AF: 0.00782 AC: 1959 AN: 250446 Hom.: 22 AF XY: 0.00848 AC XY: 1148 AN XY: 135416

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00444

Gnomad ASJ exome AF: 0.00905

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00798

Gnomad FIN exome AF: 0.0243

Gnomad NFE exome AF: 0.00773

Gnomad OTH exome AF: 0.00706

GnomAD4 exome AF: 0.00805 AC: 11764 AN: 1461076 Hom.: 79 Cov.: 31 AF XY: 0.00819 AC XY: 5949 AN XY: 726794

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00414

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00780

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.00801

Gnomad4 OTH exome AF: 0.00882

GnomAD4 genome AF: 0.00703 AC: 1071 AN: 152266 Hom.: 6 Cov.: 32 AF XY: 0.00770 AC XY: 573 AN XY: 74458

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.00823

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.00701 Hom.: 3

Bravo AF: 0.00508

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.00900

EpiControl AF: 0.00806

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MRPS14: BP4, BP7, BS2 -

MRPS14-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.023
DANN	Benign	0.58
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

Other links and lift over

dbSNP: rs36081614; hg19: chr1-174983841; COSMIC: COSV100871582; COSMIC: COSV100871582;