rs7322754

Variant names:

• chr13-40748841-G-T
• rs7322754
• NM_005830.4:c.958+297C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005830.4(MRPS31):​c.958+297C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,080 control chromosomes in the GnomAD database, including 3,806 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 0.21 (3806 hom., cov: 33)
• Consequence: MRPS31 NM_005830.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 7 publications found

Genes affected

MRPS31 (HGNC:16632): (mitochondrial ribosomal protein S31) 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. The 28S subunit of the mammalian mitoribosome may play a crucial and characteristic role in translation initiation. This gene encodes a 28S subunit protein that has also been associated with type 1 diabetes; however, its relationship to the etiology of this disease remains to be clarified. Pseudogenes corresponding to this gene have been found on chromosomes 3 and 13. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005830.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS31	NM_005830.4	MANE Select	c.958+297C>A		intron	N/A	NP_005821.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS31	ENST00000323563.8	TSL:1 MANE Select	c.958+297C>A		intron	N/A	ENSP00000315397.6
	MRPS31	ENST00000461675.1	TSL:2	n.279+297C>A		intron	N/A
	MRPS31	ENST00000498078.1	TSL:2	n.476+297C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31783 AN: 151962 Hom.: 3804 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31787 AN: 152080 Hom.: 3806 Cov.: 33 AF XY: 0.201 AC XY: 14942 AN XY: 74314

African (AFR) AF: 0.105 AC: 4344 AN: 41508

American (AMR) AF: 0.169 AC: 2587 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.120 AC: 620 AN: 5178

South Asian (SAS) AF: 0.184 AC: 884 AN: 4806

European-Finnish (FIN) AF: 0.204 AC: 2153 AN: 10556

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19671 AN: 67954

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.258 Hom.: 8872

Bravo AF: 0.201

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.26
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: rs7322754; hg19: chr13-41322977;