Variant chr8-93780845-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153704.6(TMEM67):c.870-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,595,426 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 62 hom. )

Consequence

TMEM67
NM_153704.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0260

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 8-93780845-A-G is Benign according to our data. Variant chr8-93780845-A-G is described in ClinVar as [Benign]. Clinvar id is 126308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM67	NM_153704.6 link	c.870-29A>G		intron_variant	Intron 8 of 27	ENST00000453321.8	NP_714915.3	Q5HYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM67	ENST00000453321.8 link	c.870-29A>G		intron_variant	Intron 8 of 27	1	NM_153704.6	ENSP00000389998.3		Q5HYA8

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2743

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00456

AC:

1142

AN:

250452

Hom.:

AF XY:

0.00342

AC XY:

464

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.0641

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000794

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00169

AC:

2441

AN:

1443114

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1033

AN XY:

718712

show subpopulations

Gnomad4 AFR exome

AF:

0.0619

Gnomad4 AMR exome

AF:

0.00327

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000337

Gnomad4 OTH exome

AF:

0.00329

GnomAD4 genome

AF:

0.0180

AC:

2744

AN:

152312

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1281

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00928

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over