chr17-28720857-A-G

Variant names:

• chr17-28720857-A-G
• rs61738395
• NM_000984.6:c.176A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000984.6(RPL23A):​c.176A>G​(p.Lys59Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,614,058 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. K59T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: RPL23A NM_000984.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.16
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012814105).
• BS2: High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL23A	NM_000984.6	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 5	ENST00000422514.7	NP_000975.2
SNORD42B	NR_000013.1	n.*241A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL23A	ENST00000422514.7	c.176A>G	p.Lys59Arg	missense_variant	Exon 2 of 5	1	NM_000984.6	ENSP00000389103.2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152126 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000468 AC: 117 AN: 250224 AF XY: 0.000568

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000240 AC: 351 AN: 1461814 Hom.: 3 Cov.: 31 AF XY: 0.000340 AC XY: 247 AN XY: 727216

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00361 AC: 311 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111954

Other (OTH) AF: 0.000248 AC: 15 AN: 60390

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152244 Hom.: 2 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74440

African (AFR) AF: 0.0000481 AC: 2 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000150 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.000552 AC: 67

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.013	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.3	M;.;.
PhyloP100		9.2
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.2	N;N;.
REVEL	Benign	0.26
Sift	Benign	0.099	T;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.043	B;.;.
Vest4		0.64
MutPred		0.42		Loss of methylation at K59 (P = 0.0083);.;.;
MVP		0.51
MPC		0.80
ClinPred		0.068	T
GERP RS		5.8
PromoterAI		0.041	Neutral
Varity_R		0.15
gMVP		0.36
Mutation Taster		=220/80	polymorphism

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: rs61738395; hg19: chr17-27047875;