11-111937554-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.90

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIXDC1	NM_001037954.4	c.55A>G	p.Asn19Asp	missense_variant	1/20	ENST00000440460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIXDC1	ENST00000440460.7	c.55A>G	p.Asn19Asp	missense_variant	1/20	1	NM_001037954.4	P1
DIXDC1	ENST00000529225.5	c.57+7644A>G		intron_variant		5
DIXDC1	ENST00000528399.1	n.135A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.000961 AC: 146 AN: 151966 Hom.: 0 Cov.: 32

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.: 4 AF XY: 0.00196 AC XY: 222 AN XY: 113110

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.: 6 Cov.: 31 AF XY: 0.000630 AC XY: 450 AN XY: 714238

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.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 84 AN XY: 74370

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.: 0

Bravo AF: 0.00144

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00182 AC: 219

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	D;N;N
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.067
Sift	Benign	0.10	T
Sift4G	Benign	0.58	T
Polyphen		0.023	B
Vest4		0.26
MVP		0.56
MPC		0.22
ClinPred		0.060	T
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

Other links and lift over

dbSNP: rs199945833; hg19: chr11-111808278; COSMIC: COSV67742360;