Genetic Variant UBIAD1:p.Asn102Ser (chr1-11273836-A-G) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_013319.3(UBIAD1):c.305A>G(p.Asn102Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBIAD1
NM_013319.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.65

Publications

38 publications found

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]

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

UBIAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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, 0.991

PP5

Variant 1-11273836-A-G is Pathogenic according to our data. Variant chr1-11273836-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 856.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 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 2	ENST00000376810.6	NP_037451.1	Q9Y5Z9-1
UBIAD1	NM_001330349.2 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 3		NP_001317278.1
UBIAD1	NM_001330350.2 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 2		NP_001317279.1	Q9Y5Z9-2
UBIAD1	XM_047418727.1 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBIAD1	ENST00000376810.6 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 2	1	NM_013319.3	ENSP00000366006.5	Q9Y5Z9-1
UBIAD1	ENST00000376804.2 link	c.305A>G	p.Asn102Ser	missense_variant	Exon 1 of 2	2		ENSP00000366000.1	Q9Y5Z9-2
UBIAD1	ENST00000483738.1 link	c.-98A>G		upstream_gene_variant		3		ENSP00000473453.1	R4GN21
UBIAD1	ENST00000486588.6 link	n.-53A>G		upstream_gene_variant		5		ENSP00000473612.1	R4GNE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00228

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Schnyder crystalline corneal dystrophy

Pathogenic:1

Feb 01, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.2

M;M

PhyloP100

8.6

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.1

D;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.98

MutPred

0.95

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.94

MPC

1.3

ClinPred

1.0

GERP RS

3.9

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.77

gMVP

0.92

Mutation Taster

=24/76

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over