12-47964282-C-T

Variant names:

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

Variant summary

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

The NM_001143842.2(TMEM106C):​c.46C>T​(p.Arg16*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TMEM106C NM_001143842.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Arg16*	stop_gained	Exon 2 of 8	NP_001137314.1	Q9BVX2-1
	TMEM106C	NM_024056.4		c.46C>T	p.Arg16*	stop_gained	Exon 2 of 8	NP_076961.1	Q9BVX2-1
	TMEM106C	NM_001143841.2		c.46C>T	p.Arg16*	stop_gained	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>T	p.Arg16*	stop_gained	Exon 2 of 8	ENSP00000400471.2	Q9BVX2-1
	TMEM106C	ENST00000552561.5	TSL:1	c.46C>T	p.Arg16*	stop_gained	Exon 2 of 8	ENSP00000446657.1	Q9BVX2-1
	TMEM106C	ENST00000256686.10	TSL:1	c.46C>T	p.Arg16*	stop_gained	Exon 2 of 8	ENSP00000256686.6	Q9BVX2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250748 AF XY: 0.0000221

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461624 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44692

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111886

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.044
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.10	N
PhyloP100		-0.19
Vest4		0.22
GERP RS		2.5
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=41/159	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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;