15-88467998-C-T

Variant names:

• chr15-88467998-C-T
• rs1186725832
• NM_022839.5:c.156C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321972.2(MRPS11):​c.-1071C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MRPS11 NM_001321972.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 0 publications found

Genes affected

MRPS11 (HGNC:14050): (mitochondrial ribosomal protein S11) 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 contains a high level of sequence similarity with ribosomal protein S11P family members. A pseudogene corresponding to this gene is found on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

ENSG00000173867 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321972.2. 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
	MRPS11	NM_022839.5	MANE Select	c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 6	NP_073750.2
	MRPS11	NM_001321972.2		c.-1071C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001308901.1
	MRPS11	NM_001321976.2		c.-1071C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001308905.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS11	ENST00000325844.9	TSL:1 MANE Select	c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 6	ENSP00000317376.4	P82912-1
	MRPS11	ENST00000353598.6	TSL:1	c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 5	ENSP00000318054.7	P82912-3
	ENSG00000173867	ENST00000649547.1		c.*756-2225G>A		intron	N/A	ENSP00000497509.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 233934 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454792 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723168

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39204

South Asian (SAS) AF: 0.00 AC: 0 AN: 85094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109166

Other (OTH) AF: 0.00 AC: 0 AN: 60034

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.40
PromoterAI		-0.0089	Neutral
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

Other links and lift over

dbSNP: rs1186725832; hg19: chr15-89011229;