chr7-12233526-A-C

Variant names:

• chr7-12233526-A-C
• rs14978
• NM_001134232.2:c.*1551A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134232.2(TMEM106B):​c.*1551A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: TMEM106B NM_001134232.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.*1551A>C		3_prime_UTR	Exon 8 of 8	NP_001127704.1	Q9NUM4
	TMEM106B	NM_018374.4		c.*1551A>C		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.*1551A>C		3_prime_UTR	Exon 8 of 8	ENSP00000379902.3	Q9NUM4
	TMEM106B	ENST00000396667.7	TSL:1	c.*1551A>C		3_prime_UTR	Exon 9 of 9	ENSP00000379901.2	Q9NUM4
	TMEM106B	ENST00000444443.6	TSL:4	c.*1551A>C		3_prime_UTR	Exon 8 of 8	ENSP00000401302.2	Q9NUM4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.31
DANN	Benign	0.79
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs14978; hg19: chr7-12273152;