14-44963101-A-T

Variant summary

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

The NM_001308120.2(TOGARAM1):​c.680A>T​(p.Asp227Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TOGARAM1
NM_001308120.2 missense

Scores

3
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57
Variant links:
Genes affected
TOGARAM1 (HGNC:19959): (TOG array regulator of axonemal microtubules 1) Predicted to enable microtubule binding activity. Predicted to be involved in organelle assembly and positive regulation of microtubule polymerization. Predicted to be located in ciliary basal body. Predicted to be active in cilium and microtubule cytoskeleton. Predicted to colocalize with microtubule. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]
KLHL28 (HGNC:19741): (kelch like family member 28)

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 rank MANE Protein UniProt
TOGARAM1NM_001308120.2 linkc.680A>T p.Asp227Val missense_variant Exon 1 of 20 ENST00000361462.7 NP_001295049.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOGARAM1ENST00000361462.7 linkc.680A>T p.Asp227Val missense_variant Exon 1 of 20 1 NM_001308120.2 ENSP00000354917.2 G3XAE9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251486
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727246
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.076
T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Benign
-0.60
T
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.0
D;N
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.61
MutPred
0.35
Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);
MVP
0.67
MPC
0.71
ClinPred
0.95
D
GERP RS
5.0
Varity_R
0.45
gMVP
0.44

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.

Other links and lift over

dbSNP: rs755101967; hg19: chr14-45432304; API