11-111974908-C-A

Variant names:

• chr11-111974908-C-A
• rs930647209
• NM_001037954.4:c.581C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001037954.4(DIXDC1):​c.581C>A​(p.Pro194Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P194L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: DIXDC1 NM_001037954.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• 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.581C>A	p.Pro194Gln	missense	Exon 5 of 20	NP_001033043.1	Q155Q3-1
	DIXDC1	NM_001278542.2		c.578C>A	p.Pro193Gln	missense	Exon 6 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.581C>A	p.Pro194Gln	missense	Exon 5 of 20	ENSP00000394352.3	Q155Q3-1
	DIXDC1	ENST00000941466.1		c.581C>A	p.Pro194Gln	missense	Exon 5 of 19	ENSP00000611525.1
	DIXDC1	ENST00000529225.5	TSL:5	c.578C>A	p.Pro193Gln	missense	Exon 6 of 6	ENSP00000434130.1	Q155Q3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461486 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.1
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.37		Loss of helix (P = 0.0072)
MVP		0.95
MPC		0.74
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.63
Mutation Taster		=68/32	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: rs930647209; hg19: chr11-111845632;