rs587779735

chr8-93755751-CTTTTTTTTTTTT-Cchr8-93755751-CTTTTTTTTTTTT-CTchr8-93755751-CTTTTTTTTTTTT-CTTchr8-93755751-CTTTTTTTTTTTT-CTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTGTAATTTTATGTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTchr8-93755751-CTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153704.6(TMEM67):c.224-14_224-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000073 in 547,780 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: 28)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: TMEM67 NM_153704.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

TMEM67 (HGNC:28396): (transmembrane protein 67) The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Meckel syndrome type 3 (MKS3) and Joubert syndrome type 6 (JBTS6). [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM67	NM_153704.6	c.224-14_224-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000453321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM67	ENST00000453321.8	c.224-14_224-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_153704.6	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000730 AC: 4 AN: 547780 Hom.: 0 AF XY: 0.00000690 AC XY: 2 AN XY: 289910

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000795

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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: rs587779735; hg19: chr8-94767979;