rs13234238

chr7-12229587-A-Cchr7-12229587-A-G

Variant summary

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

The NM_001134232.2(TMEM106B):c.442-92A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 1,039,812 control chromosomes in the GnomAD database, including 3,272 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 0.056 (334 hom., cov: 33)
  • Exomes 𝑓: 0.076 (2938 hom.)
• Consequence: TMEM106B NM_001134232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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 (NFE) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM106B	NM_001134232.2	c.442-92A>C		intron_variant		ENST00000396668.8
TMEM106B	NM_018374.4	c.442-92A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM106B	ENST00000396668.8	c.442-92A>C		intron_variant		1	NM_001134232.2	P1

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8565 AN: 152058 Hom.: 334 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0576

GnomAD4 exome AF: 0.0763 AC: 67698 AN: 887638 Hom.: 2938 AF XY: 0.0752 AC XY: 33320 AN XY: 443128

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.0787

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.0253

Gnomad4 FIN exome AF: 0.0505

Gnomad4 NFE exome AF: 0.0874

Gnomad4 OTH exome AF: 0.0723

GnomAD4 genome AF: 0.0563 AC: 8567 AN: 152174 Hom.: 334 Cov.: 33 AF XY: 0.0554 AC XY: 4123 AN XY: 74414

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0497

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.0570

Alfa AF: 0.0259 Hom.: 15

Bravo AF: 0.0559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.7
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs13234238; hg19: chr7-12269213;