12-112405271-C-T

Variant names:

• chr12-112405271-C-T
• rs973688075
• NM_000970.6:c.820G>A

Variant summary

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

The NM_000970.6(RPL6):​c.820G>A​(p.Val274Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,602 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPL6 NM_000970.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.388
• Publications: 0 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: 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=0.10766482).

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.820G>A	p.Val274Met	missense	Exon 7 of 7	NP_000961.2
	RPL6	NM_001024662.3		c.820G>A	p.Val274Met	missense	Exon 7 of 7	NP_001019833.1	Q02878
	RPL6	NM_001320137.2		c.820G>A	p.Val274Met	missense	Exon 7 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.820G>A	p.Val274Met	missense	Exon 7 of 7	ENSP00000202773.9	Q02878
	RPL6	ENST00000424576.6	TSL:1	c.820G>A	p.Val274Met	missense	Exon 7 of 7	ENSP00000403172.2	Q02878
	RPL6	ENST00000935343.1		c.898G>A	p.Val300Met	missense	Exon 7 of 7	ENSP00000605402.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454602 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723630

African (AFR) AF: 0.00 AC: 0 AN: 32942

American (AMR) AF: 0.00 AC: 0 AN: 42918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4284

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110040

Other (OTH) AF: 0.00 AC: 0 AN: 60004

GnomAD4 genome Cov.: 33

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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.7
DANN	Benign	0.83
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.39
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.012
Sift	Benign	0.30	T
Sift4G	Benign	0.18	T
Polyphen		0.0040	B
Vest4		0.15
MutPred		0.32		Gain of helix (P = 0.1736)
MVP		0.38
MPC		0.87
ClinPred		0.037	T
GERP RS		-0.37
Varity_R		0.034
gMVP		0.14
Mutation Taster		=97/3	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: rs973688075; hg19: chr12-112843075;