8-93755751-CTTTTTTTTTTTT-CTTTT

Position:

• chr8-93755751-CTTTTTTTTTTTT-CTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_153704.6(TMEM67):​c.224-10_224-3delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 633,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: TMEM67 NM_153704.6 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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]

TMEM67 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-93755751-CTTTTTTTT-C is Benign according to our data. Variant chr8-93755751-CTTTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3352454.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM67	NM_153704.6	c.224-10_224-3delTTTTTTTT		splice_region_variant, intron_variant		ENST00000453321.8	NP_714915.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM67	ENST00000453321.8	c.224-10_224-3delTTTTTTTT		splice_region_variant, intron_variant		1	NM_153704.6	ENSP00000389998.3

Frequencies

GnomAD3 genomes AF: 0.0000469 AC: 4 AN: 85340 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000457

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000481

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000694 AC: 38 AN: 547774 Hom.: 0 AF XY: 0.0000586 AC XY: 17 AN XY: 289906

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000245

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000715

Gnomad4 OTH exome AF: 0.000122

GnomAD4 genome AF: 0.0000469 AC: 4 AN: 85340 Hom.: 0 Cov.: 28 AF XY: 0.0000249 AC XY: 1 AN XY: 40174

Gnomad4 AFR AF: 0.0000457

Gnomad4 AMR AF: 0.000120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000481

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TMEM67-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;