rs118203952

Positions:

• chr1-11285670-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_013319.3(UBIAD1):​c.556G>A​(p.Gly186Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBIAD1 NM_013319.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.56

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 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986
• PP5: Variant 1-11285670-G-A is Pathogenic according to our data. Variant chr1-11285670-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 863.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-11285670-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBIAD1	NM_013319.3	c.556G>A	p.Gly186Arg	missense_variant	2/2	ENST00000376810.6
UBIAD1	NM_001330349.2	c.556G>A	p.Gly186Arg	missense_variant	2/3
UBIAD1	XM_047418727.1	c.556G>A	p.Gly186Arg	missense_variant	2/3
UBIAD1	NM_001330350.2	c.530-9203G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBIAD1	ENST00000376810.6	c.556G>A	p.Gly186Arg	missense_variant	2/2	1	NM_013319.3	P1
UBIAD1	ENST00000483738.1	c.154G>A	p.Gly52Arg	missense_variant	2/3	3
UBIAD1	ENST00000376804.2	c.530-9203G>A		intron_variant		2
UBIAD1	ENST00000486588.6	c.199G>A	p.Gly67Arg	missense_variant, NMD_transcript_variant	2/5	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

Feb 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.95	D;.
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.5	H;.
MutationTaster	Benign	1.0	A;A
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-7.4	D;.
REVEL	Pathogenic	0.94
Sift	Benign	0.051	T;.
Sift4G	Benign	0.072	T;D
Polyphen		1.0	D;.
Vest4		0.99
MutPred		0.92		Loss of ubiquitination at K181 (P = 0.1202);.;
MVP		0.99
MPC		1.6
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.99

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: rs118203952; hg19: chr1-11345727;