16-89561352-G-T

Variant names:

• chr16-89561352-G-T
• NM_000977.4:c.230G>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000977.4(RPL13):​c.230G>T​(p.Ser77Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPL13 NM_000977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74

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 5 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RL13_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4	c.230G>T	p.Ser77Ile	missense_variant	Exon 3 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.230G>T	p.Ser77Ile	missense_variant	Exon 2 of 5		NP_150254.1
RPL13	NM_001243131.1	c.230G>T	p.Ser77Ile	missense_variant	Exon 3 of 7		NP_001230060.1
SNORD68	NR_002450.1	n.-78G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.230G>T	p.Ser77Ile	missense_variant	Exon 3 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453590 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2 AN XY: 723322

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.0	M;M;M;.;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.7	D;D;D;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.73	P;P;.;.;P
Vest4		0.83
MutPred		0.78		Loss of disorder (P = 0.055);Loss of disorder (P = 0.055);Loss of disorder (P = 0.055);Loss of disorder (P = 0.055);Loss of disorder (P = 0.055);
MVP		0.39
MPC		0.91
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.94
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-89627760;