rs35245221

Positions:

chr11-61366177-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016464.5(TMEM138):c.261G>A(p.Val87Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,614,164 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 31)

Exomes 𝑓: 0.0042 ( 121 hom. )

Consequence

TMEM138
NM_016464.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0440

Variant links:

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 links:

TMEM138 (HGNC:):

TMEM138 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 11-61366177-G-A is Benign according to our data. Variant chr11-61366177-G-A is described in ClinVar as [Benign]. Clinvar id is 130586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61366177-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.044 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM138	NM_016464.5 linkuse as main transcript	c.261G>A	p.Val87Val	synonymous_variant	3/5	ENST00000278826.11	NP_057548.1	Q9NPI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM138	ENST00000278826.11 linkuse as main transcript	c.261G>A	p.Val87Val	synonymous_variant	3/5	1	NM_016464.5	ENSP00000278826.5		Q9NPI0-1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2755

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00834

AC:

2096

AN:

251440

Hom.:

AF XY:

0.00818

AC XY:

1111

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0558

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00364

Gnomad SAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00422

AC:

6175

AN:

1461846

Hom.:

121

Cov.:

AF XY:

0.00457

AC XY:

3323

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0589

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.00937

GnomAD4 genome

AF:

0.0182

AC:

2767

AN:

152318

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0563

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0196

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00308

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 16

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 20, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.6

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over