chr2-201628160-TA-T

Variant names:

• chr2-201628160-TA-T
• rs555284377
• NM_001044385.3:c.870-12delT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001044385.3(TMEM237):​c.870-12delT variant causes a intron change. The variant allele was found at a frequency of 0.000000697 in 1,433,738 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TMEM237 NM_001044385.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• Publications: 0 publications found

Genes affected

TMEM237 (HGNC:14432): (transmembrane protein 237) The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TMEM237 Gene-Disease associations (from GenCC):

• Joubert syndrome 14

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with renal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044385.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM237	NM_001044385.3	MANE Select	c.870-12delT		intron	N/A	NP_001037850.1	Q96Q45-1
	TMEM237	NM_152388.4		c.846-12delT		intron	N/A	NP_689601.2	Q96Q45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM237	ENST00000409883.7	TSL:5 MANE Select	c.870-12delT		intron	N/A	ENSP00000386264.2	Q96Q45-1
	TMEM237	ENST00000621467.5	TSL:1	c.744-12delT		intron	N/A	ENSP00000480508.2	A0A087WWU1
	TMEM237	ENST00000466641.5	TSL:1	n.568-12delT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433738 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 711536

African (AFR) AF: 0.00 AC: 0 AN: 32834

American (AMR) AF: 0.00 AC: 0 AN: 41888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39044

South Asian (SAS) AF: 0.00 AC: 0 AN: 82466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095040

Other (OTH) AF: 0.00 AC: 0 AN: 59258

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs555284377; hg19: chr2-202492883;