9-127447894-C-T

Variant names:

• chr9-127447894-C-T
• rs1315505033
• NM_000976.4:c.475G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000976.4(RPL12):​c.475G>A​(p.Ala159Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPL12 NM_000976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

Genes affected

RPL12 (HGNC:10302): (ribosomal protein L12) 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 L11P family of ribosomal proteins. It is located in the cytoplasm. The protein binds directly to the 26S rRNA. This gene is co-transcribed with the U65 snoRNA, which is located in its fourth intron. 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]

ZNF79 (HGNC:13153): (zinc finger protein 79) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13495511).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000976.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL12	NM_000976.4	MANE Select	c.475G>A	p.Ala159Thr	missense	Exon 6 of 7	NP_000967.1	P30050-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL12	ENST00000361436.10	TSL:1 MANE Select	c.475G>A	p.Ala159Thr	missense	Exon 6 of 7	ENSP00000354739.5	P30050-1
	RPL12	ENST00000536368.1	TSL:1	c.376G>A	p.Ala126Thr	missense	Exon 5 of 6	ENSP00000441179.1	P30050-2
	RPL12	ENST00000886311.1		c.550G>A	p.Ala184Thr	missense	Exon 6 of 7	ENSP00000556370.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000799 AC: 2 AN: 250300 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460806 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726616

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 85980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111556

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Benign	0.29	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.20		Gain of glycosylation at A159 (P = 0.1147)
MVP		0.58
MPC		0.64
ClinPred		0.24	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.30
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1315505033; hg19: chr9-130210173;