chr11-111968615-G-A

Variant names:

• chr11-111968615-G-A
• rs782259747
• NM_001037954.4:c.293G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037954.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIXDC1	NM_001037954.4	MANE Select	c.293G>A	p.Arg98His	missense	Exon 3 of 20	NP_001033043.1	Q155Q3-1
	DIXDC1	NM_001278542.2		c.290G>A	p.Arg97His	missense	Exon 4 of 6	NP_001265471.1	Q155Q3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIXDC1	ENST00000440460.7	TSL:1 MANE Select	c.293G>A	p.Arg98His	missense	Exon 3 of 20	ENSP00000394352.3	Q155Q3-1
	DIXDC1	ENST00000941466.1		c.293G>A	p.Arg98His	missense	Exon 3 of 19	ENSP00000611525.1
	DIXDC1	ENST00000529225.5	TSL:5	c.290G>A	p.Arg97His	missense	Exon 4 of 6	ENSP00000434130.1	Q155Q3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000247 AC: 6 AN: 242740 AF XY: 0.0000228

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110248

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.1
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.053	T
Sift4G	Benign	0.069	T
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
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs782259747; hg19: chr11-111839339;