dbSNP rs1554972391: TMEM216:p.Met1_Arg4del (chr11-61392606-TGCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACG-T) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001173990.3(TMEM216):c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG(p.Met1_Arg4del) variant causes a start lost, conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM216
NM_001173990.3 start_lost, conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.84

Publications

0 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):

ciliopathy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PVS1

Start lost variant, no new inframe start found.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173990.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM216	NM_001173990.3	MANE Select	c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG	p.Met1_Arg4del	start_lost conservative_inframe_deletion	Exon 1 of 5	NP_001167461.1	Q9P0N5-1
TMEM216	NM_001173990.3	MANE Select	c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG		5_prime_UTR	Exon 1 of 5	NP_001167461.1	Q9P0N5-1
TMEM216	NM_001173991.3		c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG	p.Met1_Arg4del	start_lost conservative_inframe_deletion	Exon 1 of 5	NP_001167462.1	Q9P0N5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM216	ENST00000515837.7	TSL:2 MANE Select	c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG	p.Met1_Arg4del	start_lost conservative_inframe_deletion	Exon 1 of 5	ENSP00000440638.1	Q9P0N5-1
TMEM216	ENST00000334888.10	TSL:2	c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG	p.Met1_Arg4del	start_lost conservative_inframe_deletion	Exon 1 of 5	ENSP00000334844.5	Q9P0N5-3
TMEM216	ENST00000515837.7	TSL:2 MANE Select	c.-24_12delCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACGG		5_prime_UTR	Exon 1 of 5	ENSP00000440638.1	Q9P0N5-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Joubert syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over