chr14-44962453-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308120.2(TOGARAM1):ā€‹c.32T>Cā€‹(p.Leu11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,582,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

TOGARAM1
NM_001308120.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.561
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.099170625).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOGARAM1NM_001308120.2 linkc.32T>C p.Leu11Pro 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.32T>C p.Leu11Pro missense_variant Exon 1 of 20 1 NM_001308120.2 ENSP00000354917.2 G3XAE9

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000665
AC:
15
AN:
225716
Hom.:
0
AF XY:
0.0000651
AC XY:
8
AN XY:
122904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000322
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000135
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
43
AN:
1430390
Hom.:
0
Cov.:
31
AF XY:
0.0000310
AC XY:
22
AN XY:
709306
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000244
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:
0.0000356
Gnomad4 OTH exome
AF:
0.0000339
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000618
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000989
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.32T>C (p.L11P) alteration is located in exon 1 (coding exon 1) of the FAM179B gene. This alteration results from a T to C substitution at nucleotide position 32, causing the leucine (L) at amino acid position 11 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.099
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.14
Sift
Uncertain
0.0040
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0040
B;B
Vest4
0.35
MutPred
0.27
Gain of glycosylation at L11 (P = 0.0192);Gain of glycosylation at L11 (P = 0.0192);
MVP
0.18
MPC
0.27
ClinPred
0.24
T
GERP RS
1.2
Varity_R
0.35
gMVP
0.34

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: rs201842534; hg19: chr14-45431656; API