11-111982362-C-T

Variant names:

• chr11-111982362-C-T
• rs1419374563
• NM_001037954.4:c.793C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001037954.4(DIXDC1):​c.793C>T​(p.Arg265*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: DIXDC1 NM_001037954.4 stop_gained
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.62
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-111982362-C-T is Pathogenic according to our data. Variant chr11-111982362-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 631529.Status of the report is no_assertion_criteria_provided, 0 stars.

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.793C>T	p.Arg265*	stop_gained	Exon 7 of 20	NP_001033043.1	Q155Q3-1
	DIXDC1	NM_033425.5		c.160C>T	p.Arg54*	stop_gained	Exon 3 of 16	NP_219493.1	Q155Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIXDC1	ENST00000440460.7	TSL:1 MANE Select	c.793C>T	p.Arg265*	stop_gained	Exon 7 of 20	ENSP00000394352.3	Q155Q3-1
	DIXDC1	ENST00000615255.1	TSL:1	c.160C>T	p.Arg54*	stop_gained	Exon 3 of 16	ENSP00000480808.1	Q155Q3-2
	DIXDC1	ENST00000614104.4	TSL:4	c.-90C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000479434.1	A0A087WVH1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000453 AC: 1 AN: 220510 AF XY: 0.00000826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461592 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727086

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111826

Other (OTH) AF: 0.0000166 AC: 1 AN: 60368

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Obesity (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.79	D
PhyloP100		2.6
Vest4		0.64
GERP RS		4.3
Mutation Taster		=3/197	disease causing (ClinVar)

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: rs1419374563; hg19: chr11-111853087; COSMIC: COSV105127445;