16-89561665-G-T

Variant names:

• chr16-89561665-G-T
• rs9930567
• NM_000977.4:c.334G>T

Variant summary

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

The NM_000977.4(RPL13):​c.334G>T​(p.Ala112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A112T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RPL13 NM_000977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.82

Genes affected

RPL13 (HGNC:10303): (ribosomal protein L13) 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 L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2011]

SNORD68 (HGNC:32729): (small nucleolar RNA, C/D box 68)

ACMG classification

Verdict is Uncertain_significance. Variant got 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
RPL13	NM_000977.4	c.334G>T	p.Ala112Ser	missense_variant	Exon 4 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.334G>T	p.Ala112Ser	missense_variant	Exon 3 of 5		NP_150254.1
RPL13	NM_001243131.1	c.267+67G>T		intron_variant	Intron 4 of 6		NP_001230060.1
SNORD68	NR_002450.1	n.*164G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.334G>T	p.Ala112Ser	missense_variant	Exon 4 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250942 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135794

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461538 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727052

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.8	M;M;.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.84	N;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.099	T;T;.;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.17	B;B;.;B
Vest4		0.56
MutPred		0.34		Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);
MVP		0.63
MPC		0.52
ClinPred		0.92	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.23
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs9930567; hg19: chr16-89628073;