2-105038258-C-T

Position:

• chr2-105038258-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182640.3(MRPS9):​c.135+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,594,610 control chromosomes in the GnomAD database, including 173,639 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 0.49 (18177 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155462 hom.)
• Consequence: MRPS9 NM_182640.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

MRPS9 (HGNC:14501): (mitochondrial ribosomal protein S9) 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. [provided by RefSeq, Jul 2008]

MRPS9-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS9	NM_182640.3	c.135+31C>T		intron_variant		ENST00000258455.8	NP_872578.1
MRPS9	XM_047445533.1	c.135+31C>T		intron_variant			XP_047301489.1
MRPS9-AS2	NR_110603.1	n.43+196G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS9	ENST00000258455.8	c.135+31C>T		intron_variant		1	NM_182640.3	ENSP00000258455.3
MRPS9-AS2	ENST00000456519.2	n.43+196G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73730 AN: 151788 Hom.: 18135 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.471

GnomAD3 exomes AF: 0.484 AC: 104558 AN: 216128 Hom.: 25475 AF XY: 0.477 AC XY: 55682 AN XY: 116842

Gnomad AFR exome AF: 0.536

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.656

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.461 AC: 665803 AN: 1442702 Hom.: 155462 Cov.: 38 AF XY: 0.459 AC XY: 328855 AN XY: 715794

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.486 AC: 73833 AN: 151908 Hom.: 18177 Cov.: 32 AF XY: 0.490 AC XY: 36406 AN XY: 74230

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.473

Alfa AF: 0.454 Hom.: 3436

Bravo AF: 0.482

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs3739160; hg19: chr2-105654716; COSMIC: COSV51521775;