11-61392621-TGTGGCAGCGTATGCTGCCAC-T

Variant names:

• chr11-61392621-TGTGGCAGCGTATGCTGCCAC-T
• rs1554972400
• NM_001173990.3:c.-9_11delTGGCAGCGTATGCTGCCACG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001173990.3(TMEM216):​c.-9_11delTGGCAGCGTATGCTGCCACG​(p.Met1fs) variant causes a frameshift, start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM216 NM_001173990.3 frameshift, start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 35 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM216	NM_001173990.3	c.-9_11delTGGCAGCGTATGCTGCCACG	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 5	ENST00000515837.7	NP_001167461.1
TMEM216	NM_001173990.3	c.-9_11delTGGCAGCGTATGCTGCCACG		5_prime_UTR_variant	Exon 1 of 5	ENST00000515837.7	NP_001167461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM216	ENST00000515837.7	c.-9_11delTGGCAGCGTATGCTGCCACG	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 5	2	NM_001173990.3	ENSP00000440638.1
TMEM216	ENST00000334888.10	c.-9_11delTGGCAGCGTATGCTGCCACG	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 5	2		ENSP00000334844.5
TMEM216	ENST00000515837	c.-9_11delTGGCAGCGTATGCTGCCACG		5_prime_UTR_variant	Exon 1 of 5	2	NM_001173990.3	ENSP00000440638.1
TMEM216	ENST00000334888	c.-9_11delTGGCAGCGTATGCTGCCACG		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000334844.5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 2;C1864148:Meckel syndrome, type 2 Uncertain:1

Mar 27, 2018

Counsyl

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554972400; hg19: chr11-61160093;