NM_182640.3:c.135+31C>T

Variant names:

• chr2-105038258-C-T
• rs3739160
• NM_182640.3:c.135+31C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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:40687): (MRPS9 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182640.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS9	NM_182640.3	MANE Select	c.135+31C>T		intron	N/A	NP_872578.1	P82933
	MRPS9-AS2	NR_110603.1		n.43+196G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS9	ENST00000258455.8	TSL:1 MANE Select	c.135+31C>T		intron	N/A	ENSP00000258455.3	P82933
	MRPS9	ENST00000886286.1		c.135+31C>T		intron	N/A	ENSP00000556345.1
	MRPS9	ENST00000925255.1		c.135+31C>T		intron	N/A	ENSP00000595314.1

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

GnomAD2 exomes AF: 0.484 AC: 104558 AN: 216128 AF XY: 0.477

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 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

African (AFR) AF: 0.524 AC: 17337 AN: 33086

American (AMR) AF: 0.483 AC: 20214 AN: 41888

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 10591 AN: 25688

East Asian (EAS) AF: 0.703 AC: 27320 AN: 38860

South Asian (SAS) AF: 0.441 AC: 36865 AN: 83620

European-Finnish (FIN) AF: 0.542 AC: 28162 AN: 51944

Middle Eastern (MID) AF: 0.339 AC: 1915 AN: 5648

European-Non Finnish (NFE) AF: 0.450 AC: 495993 AN: 1102320

Other (OTH) AF: 0.459 AC: 27406 AN: 59648

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

African (AFR) AF: 0.537 AC: 22272 AN: 41438

American (AMR) AF: 0.462 AC: 7055 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3408 AN: 5134

South Asian (SAS) AF: 0.470 AC: 2255 AN: 4800

European-Finnish (FIN) AF: 0.546 AC: 5753 AN: 10546

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30263 AN: 67940

Other (OTH) AF: 0.473 AC: 998 AN: 2112

Alfa AF: 0.456 Hom.: 3559

Bravo AF: 0.482

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		-0.23
PromoterAI		0.21	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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