ENST00000542946.2:c.*826T>A

Variant names:

• chr11-61367060-T-A
• rs1037448
• ENST00000542946.2:c.*826T>A

Variant summary

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

The ENST00000542946.2(TMEM138):​c.*826T>A 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: 31)
• Consequence: TMEM138 ENST00000542946.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 11 publications found

Genes affected

TMEM138 (HGNC:26944): (transmembrane protein 138) This gene encodes a multi-pass transmembrane protein. Reduced expression of this gene in mouse fibroblasts causes short cilia and failure of ciliogenesis. Expression of this gene is tightly coordinated with expression of the neighboring gene TMEM216. Mutations in this gene are associated with the autosomal recessive neurodevelopmental disorder Joubert Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

TMEM138 Gene-Disease associations (from GenCC):

• Joubert syndrome 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542946.2. 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
	TMEM138	NM_016464.5	MANE Select	c.300+844T>A		intron	N/A	NP_057548.1	Q9NPI0-1
	TMEM138	NM_001410999.1		c.300+844T>A		intron	N/A	NP_001397928.1	Q9NPI0-3
	TMEM138	NM_001441180.1		c.300+844T>A		intron	N/A	NP_001428109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM138	ENST00000542946.2	TSL:1	c.*826T>A		3_prime_UTR	Exon 3 of 3	ENSP00000445792.1	Q9NPI0-2
	TMEM138	ENST00000278826.11	TSL:1 MANE Select	c.300+844T>A		intron	N/A	ENSP00000278826.5	Q9NPI0-1
	TMEM138	ENST00000543594.6	TSL:1	n.*511+844T>A		intron	N/A	ENSP00000509354.1	A0A8I5KPN0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 68269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.47

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

Other links and lift over

dbSNP: rs1037448; hg19: chr11-61134532;