rs10488192

chr7-12237455-G-Achr7-12237455-G-T

Variant summary

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

The NM_001134232.2(TMEM106B):c.*5480G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,720 control chromosomes in the GnomAD database, including 1,968 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 0.15 (1968 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM106B	NM_001134232.2	c.*5480G>A		3_prime_UTR_variant	8/8	ENST00000396668.8
TMEM106B	NM_018374.4	c.*5480G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM106B	ENST00000396668.8	c.*5480G>A		3_prime_UTR_variant	8/8	1	NM_001134232.2	P1
TMEM106B	ENST00000396667.7	c.*5480G>A		3_prime_UTR_variant	9/9	1		P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22378 AN: 151602 Hom.: 1971 Cov.: 31

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.151

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.147 AC: 22368 AN: 151720 Hom.: 1968 Cov.: 31 AF XY: 0.148 AC XY: 10945 AN XY: 74092

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.150

Alfa AF: 0.186 Hom.: 5711

Bravo AF: 0.139

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.39
Dann	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488192; hg19: chr7-12277081;