rs6823

chr12-47968629-G-Cchr12-47968629-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM106C	NM_001143842.2	c.*400G>C		3_prime_UTR_variant	8/8	ENST00000429772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM106C	ENST00000429772.7	c.*400G>C		3_prime_UTR_variant	8/8	2	NM_001143842.2	P1
TMEM106C	ENST00000256686.10	c.*400G>C		3_prime_UTR_variant	8/8	1
TMEM106C	ENST00000449758.6	c.*400G>C		3_prime_UTR_variant	8/8	2

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

Gnomad4 AFR exome AF: 0.683

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.562

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

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.614

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.3
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6823; hg19: chr12-48362412;