7-12226362-C-T

Position:

• chr7-12226362-C-T

Variant summary

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

The ENST00000396668.8(TMEM106B):​c.441+1977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,932 control chromosomes in the GnomAD database, including 20,207 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 0.50 (20207 hom., cov: 32)
• Consequence: TMEM106B ENST00000396668.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM106B	NM_001134232.2	c.441+1977C>T		intron_variant		ENST00000396668.8	NP_001127704.1
TMEM106B	NM_018374.4	c.441+1977C>T		intron_variant			NP_060844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM106B	ENST00000396668.8	c.441+1977C>T		intron_variant		1	NM_001134232.2	ENSP00000379902	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76221 AN: 151814 Hom.: 20181 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.502 AC: 76297 AN: 151932 Hom.: 20207 Cov.: 32 AF XY: 0.504 AC XY: 37431 AN XY: 74266

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.474

Alfa AF: 0.427 Hom.: 28065

Bravo AF: 0.524

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.36

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: rs6966915; hg19: chr7-12265988;