8-80003006-C-A

Variant names:

• chr8-80003006-C-A
• NM_014018.3:c.388G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014018.3(MRPS28):​c.388G>T​(p.Asp130Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MRPS28 NM_014018.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

Genes affected

MRPS28 (HGNC:14513): (mitochondrial ribosomal protein S28) 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 has been called mitochondrial ribosomal protein S35 in the literature. [provided by RefSeq, Jul 2008]

ENSG00000276418 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS28	NM_014018.3	c.388G>T	p.Asp130Tyr	missense_variant	Exon 2 of 3	ENST00000276585.9	NP_054737.1
TPD52-MRPS28	NM_001387778.1	c.610G>T	p.Asp204Tyr	missense_variant	Exon 6 of 7		NP_001374707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS28	ENST00000276585.9	c.388G>T	p.Asp130Tyr	missense_variant	Exon 2 of 3	1	NM_014018.3	ENSP00000276585.4
ENSG00000276418	ENST00000522938.5	n.730G>T		non_coding_transcript_exon_variant	Exon 6 of 8	2		ENSP00000430858.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425814 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 707936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.8	D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.038	D;.;T;T
Sift4G	Uncertain	0.010	D;D;.;.
Polyphen		1.0	D;.;.;.
Vest4		0.57
MutPred		0.59		Gain of sheet (P = 0.0266);.;.;.;
MVP		0.59
MPC		0.24
ClinPred		1.0	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-80915241;