NM_013319.3:c.556G>A

Variant names:

• chr1-11285670-G-A
• rs118203952
• NM_013319.3:c.556G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 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. 14/22 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
• Publications: 14 publications found

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]

UBIAD1 Gene-Disease associations (from GenCC):

• Schnyder corneal dystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 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 VariationId is 863.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.556G>A	p.Gly186Arg	missense_variant	Exon 2 of 2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.556G>A	p.Gly186Arg	missense_variant	Exon 2 of 3		NP_001317278.1
UBIAD1	XM_047418727.1	c.556G>A	p.Gly186Arg	missense_variant	Exon 2 of 3		XP_047274683.1
UBIAD1	NM_001330350.2	c.530-9203G>A		intron_variant	Intron 1 of 1		NP_001317279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.556G>A	p.Gly186Arg	missense_variant	Exon 2 of 2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000483738.1	c.154G>A	p.Gly52Arg	missense_variant	Exon 2 of 3	3		ENSP00000473453.1
UBIAD1	ENST00000486588.6	n.199G>A		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000473612.1
UBIAD1	ENST00000376804.2	c.530-9203G>A		intron_variant	Intron 1 of 1	2		ENSP00000366000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Schnyder crystalline corneal dystrophy Pathogenic:1

Feb 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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;.
PhyloP100		9.6
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
Mutation Taster		=5/95	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: rs118203952; hg19: chr1-11345727;