20-3046511-C-G

Position:

• chr20-3046511-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000380325.4(MRPS26):​c.351C>G​(p.His117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPS26 ENST00000380325.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.29

Genes affected

MRPS26 (HGNC:14045): (mitochondrial ribosomal protein S26) 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. This gene lies adjacent to and downstream of the gonadotropin-releasing hormone precursor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042672455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS26	NM_030811.4	c.351C>G	p.His117Gln	missense_variant	2/4	ENST00000380325.4	NP_110438.1
MRPS26	XM_047440390.1	c.351C>G	p.His117Gln	missense_variant	2/4		XP_047296346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS26	ENST00000380325.4	c.351C>G	p.His117Gln	missense_variant	2/4	1	NM_030811.4	ENSP00000369682.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.351C>G (p.H117Q) alteration is located in exon 2 (coding exon 2) of the MRPS26 gene. This alteration results from a C to G substitution at nucleotide position 351, causing the histidine (H) at amino acid position 117 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.14
DANN	Benign	0.77
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.51	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.060
Sift	Benign	0.44	T
Sift4G	Benign	0.92	T
Polyphen		0.011	B
Vest4		0.13
MutPred		0.23		Loss of methylation at R115 (P = 0.0648);
MVP		0.23
MPC		0.62
ClinPred		0.11	T
GERP RS		-1.1
Varity_R		0.029
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3027157;