Variant 11-111974967-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001037954.4(DIXDC1):c.640G>A(p.Glu214Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DIXDC1
NM_001037954.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

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]

DIXDC1 links:

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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=0.1995886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIXDC1	NM_001037954.4 linkuse as main transcript	c.640G>A	p.Glu214Lys	missense_variant	5/20	ENST00000440460.7	NP_001033043.1	Q155Q3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIXDC1	ENST00000440460.7 linkuse as main transcript	c.640G>A	p.Glu214Lys	missense_variant	5/20	1	NM_001037954.4	ENSP00000394352.3		Q155Q3-1
DIXDC1	ENST00000529225.5 linkuse as main transcript	c.637G>A	p.Glu213Lys	missense_variant	6/6	5		ENSP00000434130.1		Q155Q3-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245926

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133268

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:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459916

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726018

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.640G>A (p.E214K) alteration is located in exon 5 (coding exon 5) of the DIXDC1 gene. This alteration results from a G to A substitution at nucleotide position 640, causing the glutamic acid (E) at amino acid position 214 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.042

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.46

.;N

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;T

Sift4G

Benign

0.10

T;T

Polyphen

0.0040

.;B

Vest4

0.23

MutPred

0.13

.;Gain of ubiquitination at E214 (P = 0.0069);

MVP

0.81

MPC

0.23

ClinPred

0.31

GERP RS

4.9

Varity_R

0.11

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over