Variant rs74712633 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153704.6(TMEM67):c.312+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00924 in 1,271,874 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 11 hom., cov: 31)

Exomes 𝑓: 0.0096 ( 119 hom. )

Consequence

TMEM67
NM_153704.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.637

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=-0.82).

BP6

Variant 8-93755896-C-G is Benign according to our data. Variant chr8-93755896-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00676 (1023/151334) while in subpopulation SAS AF= 0.028 (134/4784). AF 95% confidence interval is 0.0242. There are 11 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM67	NM_153704.6 linkuse as main transcript	c.312+30C>G		intron_variant		ENST00000453321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM67	ENST00000453321.8 linkuse as main transcript	c.312+30C>G		intron_variant		1	NM_153704.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00675

AC:

1021

AN:

151218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00124

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.00501

Gnomad ASJ

AF:

0.00808

Gnomad EAS

AF:

0.0211

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.00389

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00970

AC:

2195

AN:

226180

Hom.:

AF XY:

0.0109

AC XY:

1337

AN XY:

122834

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00343

Gnomad ASJ exome

AF:

0.00759

Gnomad EAS exome

AF:

0.0252

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00752

Gnomad OTH exome

AF:

0.00889

GnomAD4 exome

AF:

0.00957

AC:

10728

AN:

1120540

Hom.:

119

Cov.:

AF XY:

0.0103

AC XY:

5876

AN XY:

570750

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00308

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.0295

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.00343

Gnomad4 NFE exome

AF:

0.00796

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00676

AC:

1023

AN:

151334

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

529

AN XY:

73924

show subpopulations

Gnomad4 AFR

AF:

0.00124

Gnomad4 AMR

AF:

0.00501

Gnomad4 ASJ

AF:

0.00808

Gnomad4 EAS

AF:

0.0216

Gnomad4 SAS

AF:

0.0280

Gnomad4 FIN

AF:

0.00389

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.00713

Alfa

AF:

0.00752

Hom.:

Bravo

AF:

0.00652

Asia WGS

AF:

0.0270

AC:

AN:

3460

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.94

DANN

Benign

0.65

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