7-12236895-C-T

Variant names:

• chr7-12236895-C-T
• rs1047601
• NM_001134232.2:c.*4920C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134232.2(TMEM106B):​c.*4920C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,960 control chromosomes in the GnomAD database, including 1,222 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 0.12 (1222 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• Publications: 5 publications found

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]

TMEM106B Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 16

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134232.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM106B	NM_001134232.2	MANE Select	c.*4920C>T		3_prime_UTR	Exon 8 of 8	NP_001127704.1	Q9NUM4
	TMEM106B	NM_018374.4		c.*4920C>T		3_prime_UTR	Exon 9 of 9	NP_060844.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM106B	ENST00000396668.8	TSL:1 MANE Select	c.*4920C>T		3_prime_UTR	Exon 8 of 8	ENSP00000379902.3	Q9NUM4
	TMEM106B	ENST00000396667.7	TSL:1	c.*4920C>T		3_prime_UTR	Exon 9 of 9	ENSP00000379901.2	Q9NUM4
	TMEM106B	ENST00000444443.6	TSL:4	c.*4920C>T		3_prime_UTR	Exon 8 of 8	ENSP00000401302.2	Q9NUM4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18301 AN: 151842 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.120 AC: 18311 AN: 151960 Hom.: 1222 Cov.: 32 AF XY: 0.120 AC XY: 8879 AN XY: 74244

African (AFR) AF: 0.131 AC: 5441 AN: 41488

American (AMR) AF: 0.0776 AC: 1183 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3466

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2059 AN: 10522

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8788 AN: 67908

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.124 Hom.: 163

Bravo AF: 0.112

Asia WGS AF: 0.0320 AC: 110 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.41
PhyloP100		-0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1047601; hg19: chr7-12276521;