11-111993505-G-A

Position:

• chr11-111993505-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001037954.4(DIXDC1):​c.1282G>A​(p.Gly428Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 33)
• Consequence: DIXDC1 NM_001037954.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26683682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIXDC1	NM_001037954.4	c.1282G>A	p.Gly428Arg	missense_variant	13/20	ENST00000440460.7	NP_001033043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIXDC1	ENST00000440460.7	c.1282G>A	p.Gly428Arg	missense_variant	13/20	1	NM_001037954.4	ENSP00000394352.3
DIXDC1	ENST00000615255.1	c.649G>A	p.Gly217Arg	missense_variant	9/16	1		ENSP00000480808.1
DIXDC1	ENST00000526500.5	n.278G>A		non_coding_transcript_exon_variant	4/11	2
DIXDC1	ENST00000618522.4	n.635G>A		non_coding_transcript_exon_variant	7/14	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.1282G>A (p.G428R) alteration is located in exon 13 (coding exon 13) of the DIXDC1 gene. This alteration results from a G to A substitution at nucleotide position 1282, causing the glycine (G) at amino acid position 428 to be replaced by an arginine (R). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.020	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.74	T
REVEL	Benign	0.14
Sift4G	Benign	0.62	T;T
Polyphen		0.98	D;.
Vest4		0.42
MutPred		0.26		Gain of MoRF binding (P = 0.0044);.;
MVP		0.65
MPC		0.69
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.083
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr11-111864229;