rs17165746

chr7-12224099-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134232.2(TMEM106B):c.282-127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 808,874 control chromosomes in the GnomAD database, including 5,162 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 0.13 (1376 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3786 hom.)
• Consequence: TMEM106B NM_001134232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

TMEM106B (HGNC:22407): (transmembrane protein 106B) Enables ATPase binding activity. Involved in dendrite morphogenesis and lysosome localization. Located in endosome and lysosomal membrane. Implicated in hypomyelinating leukodystrophy. [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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM106B	NM_001134232.2	c.282-127T>A		intron_variant		ENST00000396668.8
TMEM106B	NM_018374.4	c.282-127T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM106B	ENST00000396668.8	c.282-127T>A		intron_variant		1	NM_001134232.2	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19239 AN: 152100 Hom.: 1374 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.101 AC: 66390 AN: 656656 Hom.: 3786 AF XY: 0.103 AC XY: 35038 AN XY: 341702

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0933

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0713

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0919

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.126 AC: 19252 AN: 152218 Hom.: 1376 Cov.: 32 AF XY: 0.126 AC XY: 9374 AN XY: 74436

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0956

Gnomad4 OTH AF: 0.122

Alfa AF: 0.108 Hom.: 132

Bravo AF: 0.126

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.44
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17165746; hg19: chr7-12263725; COSMIC: COSV67543524;