12-47968629-G-T

Variant names:

• chr12-47968629-G-T
• rs6823
• NM_001143842.2:c.*400G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001143842.2(TMEM106C):​c.*400G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 288,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: TMEM106C NM_001143842.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671
• Publications: 21 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*400G>T		3_prime_UTR	Exon 8 of 8	NP_001137314.1	Q9BVX2-1
	TMEM106C	NM_024056.4		c.*400G>T		3_prime_UTR	Exon 8 of 8	NP_076961.1	Q9BVX2-1
	TMEM106C	NM_001143841.2		c.*400G>T		3_prime_UTR	Exon 8 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.*400G>T		3_prime_UTR	Exon 8 of 8	ENSP00000400471.2	Q9BVX2-1
	TMEM106C	ENST00000256686.10	TSL:1	c.*400G>T		3_prime_UTR	Exon 8 of 8	ENSP00000256686.6	Q9BVX2-2
	TMEM106C	ENST00000892981.1		c.*400G>T		3_prime_UTR	Exon 8 of 8	ENSP00000563040.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000731 AC: 1 AN: 136714 Hom.: 0 Cov.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 73842

African (AFR) AF: 0.00 AC: 0 AN: 3888

American (AMR) AF: 0.00 AC: 0 AN: 6268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.00 AC: 0 AN: 6028

South Asian (SAS) AF: 0.00 AC: 0 AN: 25094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 508

European-Non Finnish (NFE) AF: 0.0000127 AC: 1 AN: 78952

Other (OTH) AF: 0.00 AC: 0 AN: 6862

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74176

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 1182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6823; hg19: chr12-48362412;