rs797046043

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153704.6(TMEM67):​c.271G>A​(p.Gly91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,371,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

TMEM67
NM_153704.6 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM67NM_153704.6 linkuse as main transcriptc.271G>A p.Gly91Arg missense_variant 2/28 ENST00000453321.8 NP_714915.3 Q5HYA8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM67ENST00000453321.8 linkuse as main transcriptc.271G>A p.Gly91Arg missense_variant 2/281 NM_153704.6 ENSP00000389998.3 Q5HYA8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000219
AC:
3
AN:
1371208
Hom.:
0
Cov.:
29
AF XY:
0.00000147
AC XY:
1
AN XY:
682536
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000191
Gnomad4 OTH exome
AF:
0.0000182
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 15, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.38
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.71
D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Pathogenic
2.9
M;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Pathogenic
0.78
Sift
Benign
0.039
D;D
Sift4G
Benign
0.098
T;D
Polyphen
0.98
D;.
Vest4
0.52
MutPred
0.55
Loss of stability (P = 0.2774);Loss of stability (P = 0.2774);
MVP
0.99
MPC
0.39
ClinPred
0.99
D
GERP RS
5.0
Varity_R
0.25
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs797046043; hg19: chr8-94768053; API