rs147953784

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 257597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61393214-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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

GnomAD3 exomes

AF:

0.00785

AC:

1067

AN:

135982

Hom.:

AF XY:

0.00933

AC XY:

689

AN XY:

73846

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 SAS exome

AF:

0.0225

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

Gnomad4 AFR exome

AF:

0.000762

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.00243

Gnomad4 EAS exome

AF:

0.000224

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.00322

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.00513

AC:

782

AN:

152312

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00662

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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

- -

Familial aplasia of the vermis

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

DANN

Benign

0.55

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

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