NM_022839.5:c.156C>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_022839.5(MRPS11):​c.156C>G​(p.Asn52Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MRPS11 NM_022839.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039540052).
• BP6: Variant 15-88467998-C-G is Benign according to our data. Variant chr15-88467998-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3398291.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022839.5. 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>G	p.Asn52Lys	missense	Exon 2 of 6	NP_073750.2
	MRPS11	NM_001321970.2		c.153C>G	p.Asn51Lys	missense	Exon 2 of 6	NP_001308899.1	P82912-2
	MRPS11	NM_176805.4		c.156C>G	p.Asn52Lys	missense	Exon 2 of 5	NP_789775.1	P82912-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS11	ENST00000325844.9	TSL:1 MANE Select	c.156C>G	p.Asn52Lys	missense	Exon 2 of 6	ENSP00000317376.4	P82912-1
	MRPS11	ENST00000353598.6	TSL:1	c.156C>G	p.Asn52Lys	missense	Exon 2 of 5	ENSP00000318054.7	P82912-3
	ENSG00000173867	ENST00000649547.1		c.*756-2225G>C		intron	N/A	ENSP00000497509.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.39
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.40
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.026
Sift	Benign	0.80	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.37		Gain of helix (P = 0.0082)
MVP		0.095
MPC		0.25
ClinPred		0.077	T
GERP RS		-7.9
PromoterAI		-0.027	Neutral
Varity_R		0.051
gMVP		0.22

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;