7-12236895-C-T

Position:

• chr7-12236895-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM106B	NM_001134232.2	c.*4920C>T		3_prime_UTR_variant	8/8	ENST00000396668.8	NP_001127704.1
TMEM106B	NM_018374.4	c.*4920C>T		3_prime_UTR_variant	9/9		NP_060844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM106B	ENST00000396668.8	c.*4920C>T		3_prime_UTR_variant	8/8	1	NM_001134232.2	ENSP00000379902.3
TMEM106B	ENST00000396667.7	c.*4920C>T		3_prime_UTR_variant	9/9	1		ENSP00000379901.2
TMEM106B	ENST00000444443.6	c.*4920C>T		3_prime_UTR_variant	8/8	4		ENSP00000401302.2
TMEM106B	ENST00000704417.1	c.*4920C>T		3_prime_UTR_variant	8/8			ENSP00000515893.1

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

Gnomad4 FIN exome AF: 0.00

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.114

Alfa AF: 0.124 Hom.: 154

Bravo AF: 0.112

Asia WGS AF: 0.0320 AC: 110 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047601; hg19: chr7-12276521;