chr12-47964282-C-G

Variant names:

• chr12-47964282-C-G
• rs751177758
• NM_001143842.2:c.46C>G

Variant summary

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

The NM_001143842.2(TMEM106C):​c.46C>G​(p.Arg16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: TMEM106C NM_001143842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.193
• Publications: 0 publications found

Genes affected

TMEM106C (HGNC:28775): (transmembrane protein 106C) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [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=0.07695803).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143842.2. 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
	TMEM106C	NM_001143842.2	MANE Select	c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	NP_001137314.1	Q9BVX2-1
	TMEM106C	NM_024056.4		c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	NP_076961.1	Q9BVX2-1
	TMEM106C	NM_001143841.2		c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	NP_001137313.1	Q9BVX2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM106C	ENST00000429772.7	TSL:2 MANE Select	c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	ENSP00000400471.2	Q9BVX2-1
	TMEM106C	ENST00000552561.5	TSL:1	c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	ENSP00000446657.1	Q9BVX2-1
	TMEM106C	ENST00000256686.10	TSL:1	c.46C>G	p.Arg16Gly	missense	Exon 2 of 8	ENSP00000256686.6	Q9BVX2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.19
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.053
Sift	Uncertain	0.014	D
Sift4G	Benign	0.29	T
Polyphen		0.28	B
Vest4		0.26
MutPred		0.16		Loss of stability (P = 0.0192)
MVP		0.20
MPC		0.37
ClinPred		0.17	T
GERP RS		2.5
PromoterAI		-0.088	Neutral
Varity_R		0.13
gMVP		0.34
Mutation Taster		=88/12	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: rs751177758; hg19: chr12-48358065;