rs6823

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-47968629-G-C
• chr12-47968629-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143842.2(TMEM106C):​c.*400G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 288,370 control chromosomes in the GnomAD database, including 50,498 homozygotes. 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 0.60 (27775 hom., cov: 32)
  • Exomes 𝑓: 0.56 (22723 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90869 AN: 151876 Hom.: 27738 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.563 AC: 76750 AN: 136376 Hom.: 22723 Cov.: 0 AF XY: 0.567 AC XY: 41798 AN XY: 73666

African (AFR) AF: 0.683 AC: 2651 AN: 3880

American (AMR) AF: 0.675 AC: 4226 AN: 6260

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1647 AN: 3204

East Asian (EAS) AF: 0.838 AC: 5037 AN: 6014

South Asian (SAS) AF: 0.594 AC: 14847 AN: 25006

European-Finnish (FIN) AF: 0.462 AC: 2722 AN: 5898

Middle Eastern (MID) AF: 0.571 AC: 290 AN: 508

European-Non Finnish (NFE) AF: 0.527 AC: 41481 AN: 78760

Other (OTH) AF: 0.562 AC: 3849 AN: 6846

GnomAD4 genome AF: 0.598 AC: 90957 AN: 151994 Hom.: 27775 Cov.: 32 AF XY: 0.596 AC XY: 44233 AN XY: 74270

African (AFR) AF: 0.672 AC: 27840 AN: 41436

American (AMR) AF: 0.671 AC: 10243 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4276 AN: 5182

South Asian (SAS) AF: 0.610 AC: 2939 AN: 4816

European-Finnish (FIN) AF: 0.459 AC: 4829 AN: 10530

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37069 AN: 67970

Other (OTH) AF: 0.614 AC: 1295 AN: 2108

Alfa AF: 0.435 Hom.: 1182

Bravo AF: 0.617

Asia WGS AF: 0.698 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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;