chr12-112408625-G-T

Variant names:

• chr12-112408625-G-T
• rs1454765122
• NM_000970.6:c.32C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000970.6(RPL6):​c.32C>A​(p.Thr11Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RPL6 NM_000970.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09109533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL6	NM_000970.6	c.32C>A	p.Thr11Asn	missense_variant	Exon 2 of 7	ENST00000202773.14	NP_000961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL6	ENST00000202773.14	c.32C>A	p.Thr11Asn	missense_variant	Exon 2 of 7	1	NM_000970.6	ENSP00000202773.9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T;T;T;T;T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.079	N
LIST_S2	Uncertain	0.93	.;D;D;D;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.091	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.80	N;N;.;N;N;N;N
REVEL	Benign	0.070
Sift	Uncertain	0.0070	D;D;.;D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;.;.;.;.
Polyphen		0.079	B;B;.;.;.;.;.
Vest4		0.14
MutPred		0.17		Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);Loss of phosphorylation at T11 (P = 0.0023);
MVP		0.47
MPC		0.97
ClinPred		0.10	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.25

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: rs1454765122; hg19: chr12-112846429;