1-11273983-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013319.3(UBIAD1):c.452A>G(p.Tyr151Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,614,056 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

UBIAD1
NM_013319.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.579

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055985153).

BP6

Variant 1-11273983-A-G is Benign according to our data. Variant chr1-11273983-A-G is described in ClinVar as [Benign]. Clinvar id is 291825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00156 (238/152172) while in subpopulation AFR AF= 0.0053 (220/41522). AF 95% confidence interval is 0.00472. There are 2 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UBIAD1	NM_013319.3 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/2	ENST00000376810.6
UBIAD1	NM_001330349.2 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/3
UBIAD1	NM_001330350.2 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/2
UBIAD1	XM_047418727.1 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBIAD1	ENST00000376810.6 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/2	1	NM_013319.3	P1	Q9Y5Z9-1
UBIAD1	ENST00000376804.2 linkuse as main transcript	c.452A>G	p.Tyr151Cys	missense_variant	1/2	2			Q9Y5Z9-2
UBIAD1	ENST00000483738.1 linkuse as main transcript	c.50A>G	p.Tyr17Cys	missense_variant	1/3	3
UBIAD1	ENST00000486588.6 linkuse as main transcript	c.95A>G	p.Tyr32Cys	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

238

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000380

AC:

AN:

250028

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.00455

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00430

Gnomad4 AMR exome

AF:

0.000514

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:

0.00000450

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152172

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00530

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000305

Hom.:

Bravo

AF:

0.00179

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000395

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

UBIAD1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 23, 2022

- -

Schnyder crystalline corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

Cadd

Benign

0.28

Dann

Benign

0.49

DEOGEN2

Uncertain

0.44

T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.80

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0056

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.67

N;N;.

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.060

N;N;.

REVEL

Benign

0.19

Sift

Benign

0.20

T;T;.

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.11

MVP

0.21

MPC

0.65

ClinPred

0.0039

GERP RS

-9.8

Varity_R

0.093

gMVP

0.43

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