22-50219736-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020461.4(TUBGCP6):​c.4223C>A​(p.Ala1408Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.251
Variant links:
Genes affected
TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052402943).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBGCP6NM_020461.4 linkc.4223C>A p.Ala1408Glu missense_variant Exon 18 of 25 ENST00000248846.10 NP_065194.3 Q96RT7-1
TUBGCP6XR_001755343.3 linkn.4846C>A non_coding_transcript_exon_variant Exon 18 of 20
TUBGCP6XR_007067982.1 linkn.3163C>A non_coding_transcript_exon_variant Exon 17 of 19
TUBGCP6XR_938347.3 linkn.4787C>A non_coding_transcript_exon_variant Exon 18 of 23

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBGCP6ENST00000248846.10 linkc.4223C>A p.Ala1408Glu missense_variant Exon 18 of 25 1 NM_020461.4 ENSP00000248846.5 Q96RT7-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461442
Hom.:
0
Cov.:
76
AF XY:
0.00
AC XY:
0
AN XY:
727054
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.041
DANN
Benign
0.77
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.22
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.052
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
N;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.33
N;N
REVEL
Benign
0.053
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0060
B;.
Vest4
0.20
MutPred
0.43
Gain of solvent accessibility (P = 0.0411);.;
MVP
0.19
MPC
0.13
ClinPred
0.072
T
GERP RS
-4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.073
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50658165; API