15-82538321-T-G

Variant names:

• chr15-82538321-T-G
• NM_001021.6:c.312A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001021.6(RPS17):​c.312A>C​(p.Glu104Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 0.0000021 (0 hom.)
• Consequence: RPS17 NM_001021.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

RPS17 (HGNC:10397): (ribosomal protein S17) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four 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 S17E family of ribosomal proteins and is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia 4. Alternative splicing of this gene results in multiple transcript variants. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Apr 2014]

ENSG00000260836 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16223708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS17	NM_001021.6	c.312A>C	p.Glu104Asp	missense_variant	Exon 4 of 5	ENST00000647841.1	NP_001012.1
RPS17	NR_111943.2	n.634A>C		non_coding_transcript_exon_variant	Exon 3 of 4
RPS17	NR_111944.3	n.341A>C		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS17	ENST00000647841.1	c.312A>C	p.Glu104Asp	missense_variant	Exon 4 of 5		NM_001021.6	ENSP00000498019.1
ENSG00000260836	ENST00000562833.2	c.1659A>C	p.Glu553Asp	missense_variant	Exon 12 of 13	3		ENSP00000454786.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461124 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726884

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: 0.00000270

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	0.17
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.092	T;T;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.2	.;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.44	.;T;T;.
Sift4G	Benign	0.45	.;T;T;.
Vest4		0.31, 0.28
MutPred		0.43		Gain of ubiquitination at K107 (P = 0.1235);Gain of ubiquitination at K107 (P = 0.1235);Gain of ubiquitination at K107 (P = 0.1235);.;
MVP		0.45
ClinPred		0.32	T
GERP RS		-6.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.62
gMVP		0.57

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: chr15-83207072;