Variant 1-11273836-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_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. 12/21 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)

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a transmembrane_region Helical (size 20) in uniprot entity UBIA1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_013319.3

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 id is 856.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-11273836-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBIAD1	NM_013319.3 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/3		NP_001317278.1
UBIAD1	NM_001330350.2 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/2		NP_001317279.1
UBIAD1	XM_047418727.1 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/2	1	NM_013319.3	ENSP00000366006	P1	Q9Y5Z9-1
UBIAD1	ENST00000376804.2 linkuse as main transcript	c.305A>G	p.Asn102Ser	missense_variant	1/2	2		ENSP00000366000		Q9Y5Z9-2

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 provided

literature only

OMIM

Feb 01, 2013

- -

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

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

MutationTaster

Benign

1.0

A;A

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

Varity_R

0.77

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over