chr12-47965332-C-T

Variant names:

• chr12-47965332-C-T
• rs146483924
• NM_001143842.2:c.238C>T

Variant summary

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

The NM_001143842.2(TMEM106C):​c.238C>T​(p.Arg80Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000719 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: TMEM106C NM_001143842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90
• Publications: 4 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.

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.238C>T	p.Arg80Cys	missense	Exon 3 of 8	NP_001137314.1	Q9BVX2-1
	TMEM106C	NM_024056.4		c.238C>T	p.Arg80Cys	missense	Exon 3 of 8	NP_076961.1	Q9BVX2-1
	TMEM106C	NM_001143841.2		c.238C>T	p.Arg80Cys	missense	Exon 3 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.238C>T	p.Arg80Cys	missense	Exon 3 of 8	ENSP00000400471.2	Q9BVX2-1
	TMEM106C	ENST00000552561.5	TSL:1	c.238C>T	p.Arg80Cys	missense	Exon 3 of 8	ENSP00000446657.1	Q9BVX2-1
	TMEM106C	ENST00000256686.10	TSL:1	c.238C>T	p.Arg80Cys	missense	Exon 3 of 8	ENSP00000256686.6	Q9BVX2-2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251284 AF XY: 0.0000736

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000588 AC: 86 AN: 1461582 Hom.: 0 Cov.: 30 AF XY: 0.0000619 AC XY: 45 AN XY: 727078

African (AFR) AF: 0.000508 AC: 17 AN: 33474

American (AMR) AF: 0.000112 AC: 5 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111824

Other (OTH) AF: 0.000116 AC: 7 AN: 60382

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74374

African (AFR) AF: 0.000627 AC: 26 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000362 Hom.: 0

Bravo AF: 0.000242

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.062	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.55
MVP		0.15
MPC		0.85
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.62
gMVP		0.49
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs146483924; hg19: chr12-48359115; COSMIC: COSV56742757; COSMIC: COSV56742757;