chr8-93755751-CTTTT-C

Position:

• chr8-93755751-CTTTT-C

Variant summary

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

The NM_153704.6(TMEM67):​c.224-6_224-3delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 631,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0020 (0 hom.)
• Consequence: TMEM67 NM_153704.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM67	NM_153704.6	c.224-6_224-3delTTTT		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.224-6_224-3delTTTT		splice_region_variant, intron_variant		1	NM_153704.6	ENSP00000389998.3

Frequencies

GnomAD3 genomes AF: 0.000246 AC: 21 AN: 85340 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000651

Gnomad SAS AF: 0.000389

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000289

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00201 AC: 1097 AN: 546332 Hom.: 0 AF XY: 0.00183 AC XY: 530 AN XY: 289156

Gnomad4 AFR exome AF: 0.00270

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.000659

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.000911

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.000246 AC: 21 AN: 85340 Hom.: 0 Cov.: 28 AF XY: 0.000299 AC XY: 12 AN XY: 40174

Gnomad4 AFR AF: 0.000137

Gnomad4 AMR AF: 0.000360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000653

Gnomad4 SAS AF: 0.000392

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000289

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs587779735; hg19: chr8-94767979;