rs14978

Positions:

• chr7-12233526-A-G
• chr7-12233526-A-T

Variant summary

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

The NM_001134232.2(TMEM106B):​c.*1551A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 150,740 control chromosomes in the GnomAD database, including 10,707 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 0.37 (10706 hom., cov: 29)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93

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 (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM106B	NM_001134232.2	c.*1551A>G		3_prime_UTR_variant	8/8	ENST00000396668.8	NP_001127704.1
TMEM106B	NM_018374.4	c.*1551A>G		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.*1551A>G		3_prime_UTR_variant	8/8	1	NM_001134232.2	ENSP00000379902	P1
TMEM106B	ENST00000396667.7	c.*1551A>G		3_prime_UTR_variant	9/9	1		ENSP00000379901	P1
TMEM106B	ENST00000444443.6	c.*1551A>G		3_prime_UTR_variant	8/8	4		ENSP00000401302	P1
TMEM106B	ENST00000704417.1	c.*1551A>G		3_prime_UTR_variant	8/8			ENSP00000515893

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55759 AN: 150622 Hom.: 10690 Cov.: 29

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.370 AC: 55816 AN: 150736 Hom.: 10706 Cov.: 29 AF XY: 0.373 AC XY: 27425 AN XY: 73620

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.355

Alfa AF: 0.327 Hom.: 9090

Bravo AF: 0.388

Asia WGS AF: 0.453 AC: 1572 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	0.35
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs14978; hg19: chr7-12273152;