rs771487387

Variant names:

• chr12-47966717-C-T
• rs771487387
• NM_001143842.2:c.587C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001143842.2(TMEM106C):​c.587C>T​(p.Pro196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: TMEM106C NM_001143842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.065360785).

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.587C>T	p.Pro196Leu	missense	Exon 6 of 8	NP_001137314.1	Q9BVX2-1
	TMEM106C	NM_024056.4		c.587C>T	p.Pro196Leu	missense	Exon 6 of 8	NP_076961.1	Q9BVX2-1
	TMEM106C	NM_001143841.2		c.530C>T	p.Pro177Leu	missense	Exon 6 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.587C>T	p.Pro196Leu	missense	Exon 6 of 8	ENSP00000400471.2	Q9BVX2-1
	TMEM106C	ENST00000552561.5	TSL:1	c.587C>T	p.Pro196Leu	missense	Exon 6 of 8	ENSP00000446657.1	Q9BVX2-1
	TMEM106C	ENST00000256686.10	TSL:1	c.530C>T	p.Pro177Leu	missense	Exon 6 of 8	ENSP00000256686.6	Q9BVX2-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152108 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000994 AC: 25 AN: 251488 AF XY: 0.000132

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45 AN XY: 727228

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111982

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152108 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

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

Alfa AF: 0.0000688 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000824 AC: 10

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	0.099
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.028	D
Polyphen		0.95	P
Vest4		0.38
MutPred		0.54		Gain of catalytic residue at P196 (P = 0.0196)
MVP		0.41
MPC		0.20
ClinPred		0.20	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.46
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs771487387; hg19: chr12-48360500;