chr1-11273755-C-T

Position:

chr1-11273755-C-T

Variant summary

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

The NM_013319.3(UBIAD1):c.224C>T(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,146 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 5 hom., cov: 31)

Exomes 𝑓: 0.011 ( 112 hom. )

Consequence

UBIAD1
NM_013319.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.79

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=0.006565273).

BP6

Variant 1-11273755-C-T is Benign according to our data. Variant chr1-11273755-C-T is described in ClinVar as [Benign]. Clinvar id is 291821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11273755-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00796 (1212/152312) while in subpopulation NFE AF= 0.0125 (847/68024). AF 95% confidence interval is 0.0118. There are 5 homozygotes in gnomad4. There are 559 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UBIAD1	NM_013319.3 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/2	ENST00000376810.6
UBIAD1	NM_001330349.2 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/3
UBIAD1	NM_001330350.2 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/2
UBIAD1	XM_047418727.1 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBIAD1	ENST00000376810.6 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/2	1	NM_013319.3	P1	Q9Y5Z9-1
UBIAD1	ENST00000376804.2 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	1/2	2			Q9Y5Z9-2

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1214

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00708

AC:

1780

AN:

251290

Hom.:

AF XY:

0.00711

AC XY:

966

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00749

Gnomad ASJ exome

AF:

0.00982

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0106

AC:

15503

AN:

1461834

Hom.:

112

Cov.:

AF XY:

0.0103

AC XY:

7495

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00771

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.00204

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00796

AC:

1212

AN:

152312

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

559

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00849

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00682

AC:

828

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	UBIAD1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

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

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0066

T;T

MetaSVM

Uncertain

-0.057

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.27

Sift

Benign

0.30

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.064

B;.

Vest4

0.18

MVP

0.42

MPC

0.57

ClinPred

0.019

GERP RS

5.0

Varity_R

0.22

gMVP

0.31

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