rs115933371

chr8-93780844-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153704.6(TMEM67):c.870-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,592,198 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (6 hom.)
• Consequence: TMEM67 NM_153704.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.48

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-93780844-C-T is Benign according to our data. Variant chr8-93780844-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM67	NM_153704.6	c.870-30C>T		intron_variant		ENST00000453321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM67	ENST00000453321.8	c.870-30C>T		intron_variant		1	NM_153704.6	P1

Frequencies

GnomAD3 genomes AF: 0.00429 AC: 653 AN: 152040 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00122 AC: 306 AN: 250378 Hom.: 5 AF XY: 0.000981 AC XY: 133 AN XY: 135596

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.000986

GnomAD4 exome AF: 0.000498 AC: 717 AN: 1440040 Hom.: 6 Cov.: 28 AF XY: 0.000420 AC XY: 301 AN XY: 717294

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000808

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000274

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00432 AC: 657 AN: 152158 Hom.: 4 Cov.: 32 AF XY: 0.00425 AC XY: 316 AN XY: 74398

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00307 Hom.: 1

Bravo AF: 0.00490

Asia WGS AF: 0.000578 AC: 3 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.7
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs115933371; hg19: chr8-94793072;