rs1468804

Positions:

• chr7-12235882-T-C
• chr7-12235882-T-G

Variant summary

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

The NM_001134232.2(TMEM106B):​c.*3907T>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 0.517 in 151,534 control chromosomes in the GnomAD database, including 21,483 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 0.52 (21483 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM106B	NM_001134232.2	c.*3907T>C		3_prime_UTR_variant	8/8	ENST00000396668.8
TMEM106B	NM_018374.4	c.*3907T>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM106B	ENST00000396668.8	c.*3907T>C		3_prime_UTR_variant	8/8	1	NM_001134232.2	P1
TMEM106B	ENST00000396667.7	c.*3907T>C		3_prime_UTR_variant	9/9	1		P1
TMEM106B	ENST00000444443.6	c.*3907T>C		3_prime_UTR_variant	8/8	4		P1
TMEM106B	ENST00000704417.1	c.*3907T>C		3_prime_UTR_variant	8/8

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78209 AN: 151414 Hom.: 21452 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.517 AC: 78292 AN: 151534 Hom.: 21483 Cov.: 31 AF XY: 0.519 AC XY: 38450 AN XY: 74062

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.487

Alfa AF: 0.468 Hom.: 6287

Bravo AF: 0.539

Asia WGS AF: 0.595 AC: 2063 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1468804; hg19: chr7-12275508;