rs118203950

Positions:

• chr1-11273866-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2 PM5 PP3_Strong PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.74

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]

ACMG classification

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
UBIAD1	NM_013319.3	c.335A>G	p.Asp112Gly	missense_variant	1/2	ENST00000376810.6
UBIAD1	NM_001330349.2	c.335A>G	p.Asp112Gly	missense_variant	1/3
UBIAD1	NM_001330350.2	c.335A>G	p.Asp112Gly	missense_variant	1/2
UBIAD1	XM_047418727.1	c.335A>G	p.Asp112Gly	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBIAD1	ENST00000376810.6	c.335A>G	p.Asp112Gly	missense_variant	1/2	1	NM_013319.3	P1
UBIAD1	ENST00000376804.2	c.335A>G	p.Asp112Gly	missense_variant	1/2	2
UBIAD1	ENST00000486588.6			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

Submissions by phenotype

Schnyder crystalline corneal dystrophy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 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

Other links and lift over

dbSNP: rs118203950; hg19: chr1-11333923;