Variant 11-111937554-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001037954.4(DIXDC1):c.55A>G(p.Asn19Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00069 in 1,592,196 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 6 hom. )

Consequence

DIXDC1
NM_001037954.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.90

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:

DIXDC1 (HGNC:):

DIXDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005614817).

BP6

Variant 11-111937554-A-G is Benign according to our data. Variant chr11-111937554-A-G is described in ClinVar as [Benign]. Clinvar id is 727476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIXDC1	NM_001037954.4 linkuse as main transcript	c.55A>G	p.Asn19Asp	missense_variant	1/20	ENST00000440460.7	NP_001033043.1	Q155Q3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIXDC1	ENST00000440460.7 linkuse as main transcript	c.55A>G	p.Asn19Asp	missense_variant	1/20	1	NM_001037954.4	ENSP00000394352.3	Q155Q3-1
DIXDC1	ENST00000529225.5 linkuse as main transcript	c.57+7644A>G		intron_variant		5		ENSP00000434130.1	Q155Q3-5
DIXDC1	ENST00000528399.1 linkuse as main transcript	n.135A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.000961

AC:

146

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00234

AC:

492

AN:

209848

Hom.:

AF XY:

0.00196

AC XY:

222

AN XY:

113110

show subpopulations

Gnomad AFR exome

AF:

0.000416

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000391

Gnomad SAS exome

AF:

0.000994

Gnomad FIN exome

AF:

0.000522

Gnomad NFE exome

AF:

0.000542

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000661

AC:

952

AN:

1440112

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

450

AN XY:

714238

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.000909

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.000855

GnomAD4 genome

AF:

0.000960

AC:

146

AN:

152084

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000513

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00182

AC:

219

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.20

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PROVEAN

Benign

-0.11

REVEL

Benign

0.067

Sift

Benign

0.10

Sift4G

Benign

0.58

Polyphen

0.023

Vest4

0.26

MVP

0.56

MPC

0.22

ClinPred

0.060

GERP RS

4.9

Varity_R

0.19

gMVP

0.33

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.

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