11-61392635-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_001173990.3(TMEM216):c.4C>T(p.Leu2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L2L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM216 NM_001173990.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.78

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-61392635-C-T is Benign according to our data. Variant chr11-61392635-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 502341.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM216	NM_001173990.3	c.4C>T	p.Leu2=	synonymous_variant	1/5	ENST00000515837.7
TMEM216	NM_001173991.3	c.4C>T	p.Leu2=	synonymous_variant	1/5
TMEM216	NM_001330285.2	c.-194C>T		5_prime_UTR_variant	1/5
TMEM216	NM_016499.6	c.-194C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM216	ENST00000515837.7	c.4C>T	p.Leu2=	synonymous_variant	1/5	2	NM_001173990.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 31, 2017

- -

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	15
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1554972407; hg19: chr11-61160107;