chr8-93755751-CTTTTTTTTTTTT-C

Variant names:

• chr8-93755751-CTTTTTTTTTTTT-C
• rs587779735
• NM_153704.6:c.224-14_224-3delTTTTTTTTTTTT

Variant summary

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

The NM_153704.6(TMEM67):​c.224-14_224-3delTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000073 in 547,780 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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_region, 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM67	NM_153704.6	c.224-14_224-3delTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 1 of 27	ENST00000453321.8	NP_714915.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM67	ENST00000453321.8	c.224-26_224-15delTTTTTTTTTTTT		intron_variant	Intron 1 of 27	1	NM_153704.6	ENSP00000389998.3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000896 AC: 1 AN: 11158

American (AMR) AF: 0.00 AC: 0 AN: 20424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13028

East Asian (EAS) AF: 0.00 AC: 0 AN: 23616

South Asian (SAS) AF: 0.00 AC: 0 AN: 42544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2162

European-Non Finnish (NFE) AF: 0.00000795 AC: 3 AN: 377420

Other (OTH) AF: 0.00 AC: 0 AN: 24564

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.012674), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 11

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Publications

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Other links and lift over

dbSNP: rs587779735; hg19: chr8-94767979;