15-82540071-G-A

Variant names:

• chr15-82540071-G-A
• NM_001021.6:c.65C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001021.6(RPS17):​c.65C>T​(p.Thr22Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS17 NM_001021.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS17	NM_001021.6	c.65C>T	p.Thr22Met	missense_variant	Exon 2 of 5	ENST00000647841.1	NP_001012.1
RPS17	NR_111943.2	n.387C>T		non_coding_transcript_exon_variant	Exon 1 of 4
RPS17	NR_111944.3	n.94C>T		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS17	ENST00000647841.1	c.65C>T	p.Thr22Met	missense_variant	Exon 2 of 5		NM_001021.6	ENSP00000498019.1
ENSG00000260836	ENST00000562833.2	c.1412C>T	p.Thr471Met	missense_variant	Exon 10 of 13	3		ENSP00000454786.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Diamond-Blackfan anemia 4 Uncertain:1

Apr 03, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T;T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	.;D;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.4	L;L;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.3	.;D;D;.
REVEL	Pathogenic	0.68
Sift	Benign	0.12	.;T;T;.
Sift4G	Benign	0.19	.;T;T;.
Vest4		0.54, 0.54
MutPred		0.38		Gain of MoRF binding (P = 0.076);Gain of MoRF binding (P = 0.076);Gain of MoRF binding (P = 0.076);.;
MVP		0.54
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.55

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: chr15-83208822;