Genetic Variant TMEM67:c.224-9_224-3delTTTTTTT (chr8-93755751-CTTTTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_153704.6(TMEM67):c.224-9_224-3delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000964 in 633,080 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

TMEM67
NM_153704.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
COACH syndrome 1
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Meckel syndrome, type 3
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
nephronophthisis 11
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
COACH syndrome 1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
Joubert syndrome 6
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Boichis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMEM67 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153704.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM67	NM_153704.6	MANE Select	c.224-9_224-3delTTTTTTT	splice_region intron	N/A	NP_714915.3
TMEM67	NM_001142301.1		c.-62+632_-62+638delTTTTTTT	intron	N/A	NP_001135773.1
TMEM67	NR_024522.2		n.245-9_245-3delTTTTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM67	ENST00000453321.8	TSL:1 MANE Select	c.224-9_224-3delTTTTTTT	splice_region intron	N/A	ENSP00000389998.3
TMEM67	ENST00000452276.6	TSL:1	c.224-9_224-3delTTTTTTT	splice_region intron	N/A	ENSP00000388671.2
TMEM67	ENST00000474944.5	TSL:1	n.244-9_244-3delTTTTTTT	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000141

AC:

AN:

85340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000120

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000326

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000261

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000481

Gnomad OTH

AF:

0.000847

GnomAD4 exome

AF:

0.0000895

AC:

AN:

547740

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

289894

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

11156

American (AMR)

AF:

0.0000979

AC:

AN:

20420

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

13026

East Asian (EAS)

AF:

0.0000847

AC:

AN:

23614

South Asian (SAS)

AF:

0.0000470

AC:

AN:

42540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2162

European-Non Finnish (NFE)

AF:

0.0000901

AC:

AN:

377398

Other (OTH)

AF:

0.000122

AC:

AN:

24564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000141

AC:

AN:

85340

Hom.:

Cov.:

AF XY:

0.0000996

AC XY:

AN XY:

40174

show subpopulations

African (AFR)

AF:

0.000274

AC:

AN:

21870

American (AMR)

AF:

0.000120

AC:

AN:

8312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2250

East Asian (EAS)

AF:

0.000326

AC:

AN:

3072

South Asian (SAS)

AF:

0.00

AC:

AN:

2568

European-Finnish (FIN)

AF:

0.000261

AC:

AN:

3836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.0000481

AC:

AN:

41546

Other (OTH)

AF:

0.000847

AC:

AN:

1180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-93755751-CTTTTTTTTTTTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over