Genetic Variant NM_001031.5:c.6C>G (chr19-8321536-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001031.5(RPS28):c.6C>G(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D2D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RPS28
NM_001031.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.963

Variant links:

Genes affected

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS28 links:

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

NDUFA7 links:

ENSG00000167774 (HGNC:):

ENSG00000167774 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30618855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS28	NM_001031.5 link	c.6C>G	p.Asp2Glu	missense_variant	Exon 1 of 4	ENST00000600659.3	NP_001022.1	P62857B2R4R9
RPS28	XM_047439201.1 link	c.6C>G	p.Asp2Glu	missense_variant	Exon 1 of 3		XP_047295157.1
NDUFA7	NM_005001.5 link	c.-178G>C		upstream_gene_variant		ENST00000301457.3	NP_004992.2	O95182
NDUFA7	NR_135539.2 link	n.-161G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPS28	ENST00000600659.3 link	c.6C>G	p.Asp2Glu	missense_variant	Exon 1 of 4	1	NM_001031.5	ENSP00000472469.1	P62857
NDUFA7	ENST00000301457.3 link	c.-178G>C		upstream_gene_variant		1	NM_005001.5	ENSP00000301457.1	O95182
ENSG00000167774	ENST00000598884.1 link	n.-178G>C		upstream_gene_variant		4		ENSP00000470609.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435228

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711602

show subpopulations

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:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.62

M_CAP

Benign

0.079

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.96

PrimateAI

Pathogenic

0.82

Sift4G

Uncertain

0.044

Polyphen

0.23

Vest4

0.35

MutPred

0.69

Loss of MoRF binding (P = 0.1232);

MVP

0.34

MPC

1.6

ClinPred

0.76

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.079

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over