rs147953784

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001173990.3(TMEM216):c.35-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,530,872 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 65 hom. )

Consequence

TMEM216
NM_001173990.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.113

Publications

1 publications found

Variant links:

Genes affected

TMEM216 (HGNC:25018): (transmembrane protein 216) This locus encodes a transmembrane domain-containing protein. Mutations at this locus have been associated with Meckel-Gruber Syndrome Type 2, and Joubert Syndrome 2, also known as Cerebello-oculorenal Syndrome 2. [provided by RefSeq, Aug 2010]

TMEM216 Gene-Disease associations (from GenCC):

Joubert syndrome 2
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMEM216 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-61393214-C-T is Benign according to our data. Variant chr11-61393214-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00513 (782/152312) while in subpopulation SAS AF = 0.024 (116/4830). AF 95% confidence interval is 0.0205. There are 6 homozygotes in GnomAd4. There are 419 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TMEM216	NM_001173990.3 link	c.35-17C>T	intron_variant	Intron 1 of 4	ENST00000515837.7	NP_001167461.1	Q9P0N5-1
TMEM216	NM_001173991.3 link	c.35-17C>T	intron_variant	Intron 1 of 4		NP_001167462.1	Q9P0N5-3
TMEM216	NM_016499.6 link	c.-149-17C>T	intron_variant	Intron 1 of 4		NP_057583.2	Q9P0N5-2
TMEM216	NM_001330285.2 link	c.-149-17C>T	intron_variant	Intron 1 of 4		NP_001317214.1	Q9P0N5J3QT25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM216	ENST00000515837.7 link	c.35-17C>T		intron_variant	Intron 1 of 4	2	NM_001173990.3	ENSP00000440638.1		Q9P0N5-1
TMEM216	ENST00000334888.10 link	c.35-17C>T		intron_variant	Intron 1 of 4	2		ENSP00000334844.5		Q9P0N5-3

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

783

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00785

AC:

1067

AN:

135982

AF XY:

0.00933

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00146

Gnomad EAS exome

AF:

0.000287

Gnomad FIN exome

AF:

0.00507

Gnomad NFE exome

AF:

0.00686

Gnomad OTH exome

AF:

0.00703

GnomAD4 exome

AF:

0.00577

AC:

7956

AN:

1378560

Hom.:

Cov.:

AF XY:

0.00647

AC XY:

4400

AN XY:

680562

show subpopulations

African (AFR)

AF:

0.000762

AC:

AN:

31478

American (AMR)

AF:

0.00455

AC:

162

AN:

35600

Ashkenazi Jewish (ASJ)

AF:

0.00243

AC:

AN:

25074

East Asian (EAS)

AF:

0.000224

AC:

AN:

35682

South Asian (SAS)

AF:

0.0221

AC:

1750

AN:

79036

European-Finnish (FIN)

AF:

0.00322

AC:

109

AN:

33858

Middle Eastern (MID)

AF:

0.0338

AC:

192

AN:

5676

European-Non Finnish (NFE)

AF:

0.00492

AC:

5289

AN:

1074446

Other (OTH)

AF:

0.00626

AC:

361

AN:

57710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

393

785

1178

1570

1963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00513

AC:

782

AN:

152312

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41564

American (AMR)

AF:

0.00765

AC:

117

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0240

AC:

116

AN:

4830

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00663

AC:

451

AN:

68026

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00692

Hom.:

Bravo

AF:

0.00474

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

May 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Joubert syndrome 2

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Meckel syndrome, type 2

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.5

(source)

DANN

Benign

0.55

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over