rs10488192

Variant names:

• chr7-12237455-G-A
• rs10488192
• NM_001134232.2:c.*5480G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-12237455-G-A
• chr7-12237455-G-C
• chr7-12237455-G-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.*5480G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,720 control chromosomes in the GnomAD database, including 1,968 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 0.15 (1968 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542
• Publications: 7 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM106B	NM_001134232.2	c.*5480G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000396668.8	NP_001127704.1
TMEM106B	NM_018374.4	c.*5480G>A		3_prime_UTR_variant	Exon 9 of 9		NP_060844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM106B	ENST00000396668.8	c.*5480G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001134232.2	ENSP00000379902.3
TMEM106B	ENST00000396667.7	c.*5480G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000379901.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22378 AN: 151602 Hom.: 1971 Cov.: 31

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.151

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

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.147 AC: 22368 AN: 151720 Hom.: 1968 Cov.: 31 AF XY: 0.148 AC XY: 10945 AN XY: 74092

African (AFR) AF: 0.0432 AC: 1787 AN: 41378

American (AMR) AF: 0.146 AC: 2214 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1008 AN: 5156

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4808

European-Finnish (FIN) AF: 0.170 AC: 1779 AN: 10468

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13338 AN: 67918

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.177 Hom.: 8331

Bravo AF: 0.139

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.61
PhyloP100		-0.54
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: rs10488192; hg19: chr7-12277081;