rs7322754

Positions:

• chr13-40748841-G-T

Variant summary

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

The ENST00000323563.8(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 ENST00000323563.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS31	NM_005830.4	c.958+297C>A		intron_variant		ENST00000323563.8	NP_005821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS31	ENST00000323563.8	c.958+297C>A		intron_variant		1	NM_005830.4	ENSP00000315397	P1
MRPS31	ENST00000461675.1	n.279+297C>A		intron_variant, non_coding_transcript_variant		2
MRPS31	ENST00000498078.1	n.476+297C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.202

Alfa AF: 0.264 Hom.: 7276

Bravo AF: 0.201

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.64

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: rs7322754; hg19: chr13-41322977;