rs118203950

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5

The NM_013319.3(UBIAD1):​c.335A>G​(p.Asp112Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D112N) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

UBIAD1
NM_013319.3 missense

Scores

14
3
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.74
Variant links:
Genes affected
UBIAD1 (HGNC:30791): (UbiA prenyltransferase domain containing 1) This gene encodes a protein thought to be involved in cholesterol and phospholipid metabolism. Mutations in this gene are associated with Schnyder crystalline corneal dystrophy. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.98
PP5
Variant 1-11273866-A-G is Pathogenic according to our data. Variant chr1-11273866-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-11273866-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBIAD1NM_013319.3 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/2 ENST00000376810.6
UBIAD1NM_001330349.2 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/3
UBIAD1NM_001330350.2 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/2
UBIAD1XM_047418727.1 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBIAD1ENST00000376810.6 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/21 NM_013319.3 P1Q9Y5Z9-1
UBIAD1ENST00000376804.2 linkuse as main transcriptc.335A>G p.Asp112Gly missense_variant 1/22 Q9Y5Z9-2
UBIAD1ENST00000486588.6 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Schnyder crystalline corneal dystrophy Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 01, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.95
D;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Benign
0.72
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.83
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Pathogenic
3.5
H;H
MutationTaster
Benign
1.0
A;A
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-5.7
D;D
REVEL
Pathogenic
0.87
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.97
MutPred
0.82
Loss of stability (P = 0.027);Loss of stability (P = 0.027);
MVP
0.99
MPC
1.7
ClinPred
1.0
D
GERP RS
2.5
Varity_R
0.95
gMVP
0.96

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs118203950; hg19: chr1-11333923; API