rs757478415

Variant names:

• chr17-28720805-A-C
• rs757478415
• NM_000984.6:c.124A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28720805-A-C
• chr17-28720805-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000984.6(RPL23A):​c.124A>C​(p.Thr42Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T42A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL23A NM_000984.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• Publications: 0 publications found

Genes affected

RPL23A (HGNC:10317): (ribosomal protein L23a) 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 60S subunit. The protein belongs to the L23P family of ribosomal proteins. It is located in the cytoplasm. The protein may be one of the target molecules involved in mediating growth inhibition by interferon. In yeast, the corresponding protein binds to a specific site on the 26S rRNA. This gene is co-transcribed with the U42A, U42B, U101A, and U101B small nucleolar RNA genes, which are located in its third, first, second, and fourth introns, respectively. 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]

SNORD42B (HGNC:10181): (small nucleolar RNA, C/D box 42B)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
RPL23A	NM_000984.6	c.124A>C	p.Thr42Pro	missense_variant	Exon 2 of 5	ENST00000422514.7	NP_000975.2
SNORD42B	NR_000013.1	n.*189A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL23A	ENST00000422514.7	c.124A>C	p.Thr42Pro	missense_variant	Exon 2 of 5	1	NM_000984.6	ENSP00000389103.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.5	M;.;.
PhyloP100		9.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.0070	B;.;.
Vest4		0.65
MutPred		0.44		Gain of relative solvent accessibility (P = 0.0166);.;.;
MVP		0.74
MPC		1.1
ClinPred		0.97	D
GERP RS		5.8
PromoterAI		-0.052	Neutral
Varity_R		0.71
gMVP		0.61

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

Other links and lift over

dbSNP: rs757478415; hg19: chr17-27047823;