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GeneBe

11-111968615-G-A

Variant summary

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

The NM_001037954.4(DIXDC1):c.293G>A(p.Arg98His) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,458,204 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

DIXDC1
NM_001037954.4 missense

Scores

3
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
DIXDC1 (HGNC:23695): (DIX domain containing 1) The protein encoded by this gene is a positive regulator of the Wnt signaling pathway. The encoded protein is found associated with gamma tubulin at the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

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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 UniProt
DIXDC1NM_001037954.4 linkuse as main transcriptc.293G>A p.Arg98His missense_variant 3/20 ENST00000440460.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DIXDC1ENST00000440460.7 linkuse as main transcriptc.293G>A p.Arg98His missense_variant 3/201 NM_001037954.4 P1Q155Q3-1
DIXDC1ENST00000529225.5 linkuse as main transcriptc.290G>A p.Arg97His missense_variant 4/65 Q155Q3-5
DIXDC1ENST00000528399.1 linkuse as main transcriptn.373G>A non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000247
AC:
6
AN:
242740
Hom.:
0
AF XY:
0.0000228
AC XY:
3
AN XY:
131470
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000341
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1458204
Hom.:
0
Cov.:
30
AF XY:
0.00000828
AC XY:
6
AN XY:
725038
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000248
AC:
3

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 testingAmbry GeneticsDec 02, 2022The c.293G>A (p.R98H) alteration is located in exon 3 (coding exon 3) of the DIXDC1 gene. This alteration results from a G to A substitution at nucleotide position 293, causing the arginine (R) at amino acid position 98 to be replaced by a histidine (H). 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
0.32
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.24
Cadd
Pathogenic
32
Dann
Pathogenic
1.0
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.66
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.42
T;T
MetaSVM
Benign
-0.66
T
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.24
Sift
Benign
0.053
T;D
Sift4G
Benign
0.069
T;D
Polyphen
1.0
.;D
Vest4
0.57
MutPred
0.43
.;Loss of MoRF binding (P = 0.0045);
MVP
0.78
MPC
0.86
ClinPred
0.60
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.42

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: rs782259747; hg19: chr11-111839339; API