12-112408298-G-A

Variant names:

• chr12-112408298-G-A
• rs761897821
• NM_000970.6:c.278C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_000970.6(RPL6):​c.278C>T​(p.Thr93Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T93R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RPL6 NM_000970.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• Publications: 1 publications found

Genes affected

RPL6 (HGNC:10362): (ribosomal protein L6) This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28398004).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000970.6. 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
	RPL6	NM_000970.6	MANE Select	c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	NP_000961.2
	RPL6	NM_001024662.3		c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	NP_001019833.1	Q02878
	RPL6	NM_001320137.2		c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	NP_001307066.1	Q02878

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL6	ENST00000202773.14	TSL:1 MANE Select	c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	ENSP00000202773.9	Q02878
	RPL6	ENST00000424576.6	TSL:1	c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	ENSP00000403172.2	Q02878
	RPL6	ENST00000935343.1		c.278C>T	p.Thr93Ile	missense	Exon 3 of 7	ENSP00000605402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251472 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.068
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.38	B
Vest4		0.34
MutPred		0.45		Gain of catalytic residue at P95 (P = 0.0355)
MVP		0.35
MPC		1.1
ClinPred		0.81	D
GERP RS		5.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.25
gMVP		0.44
Mutation Taster		=76/24	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: rs761897821; hg19: chr12-112846102; COSMIC: COSV104390443; COSMIC: COSV104390443;