Variant 8-93763989-G-A 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 ENST00000453321.8(TMEM67):c.506+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,170,268 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 39 hom. )

Consequence

TMEM67
ENST00000453321.8 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0930

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 8-93763989-G-A is Benign according to our data. Variant chr8-93763989-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM67	NM_153704.6 linkuse as main transcript	c.506+48G>A		intron_variant		ENST00000453321.8	NP_714915.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM67	ENST00000453321.8 linkuse as main transcript	c.506+48G>A		intron_variant		1	NM_153704.6	ENSP00000389998	P1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2452

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00413

AC:

967

AN:

234324

Hom.:

AF XY:

0.00320

AC XY:

406

AN XY:

126792

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.00361

Gnomad ASJ exome

AF:

0.000510

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00174

AC:

1771

AN:

1018034

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

773

AN XY:

526022

show subpopulations

Gnomad4 AFR exome

AF:

0.0537

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.000733

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000144

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000619

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.0162

AC:

2467

AN:

152234

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1176

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0539

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00870

Hom.:

Bravo

AF:

0.0189

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.29

DANN

Benign

0.16

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