1-11273755-C-T

Variant names:

• chr1-11273755-C-T
• rs114000606
• NM_013319.3:c.224C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 14/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.79
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 291821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1212 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013319.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBIAD1	NM_013319.3	MANE Select	c.224C>T	p.Ser75Phe	missense	Exon 1 of 2	NP_037451.1	Q9Y5Z9-1
	UBIAD1	NM_001330349.2		c.224C>T	p.Ser75Phe	missense	Exon 1 of 3	NP_001317278.1
	UBIAD1	NM_001330350.2		c.224C>T	p.Ser75Phe	missense	Exon 1 of 2	NP_001317279.1	Q9Y5Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBIAD1	ENST00000376810.6	TSL:1 MANE Select	c.224C>T	p.Ser75Phe	missense	Exon 1 of 2	ENSP00000366006.5	Q9Y5Z9-1
	UBIAD1	ENST00000376804.2	TSL:2	c.224C>T	p.Ser75Phe	missense	Exon 1 of 2	ENSP00000366000.1	Q9Y5Z9-2
	UBIAD1	ENST00000483738.1	TSL:3	c.-179C>T		upstream_gene	N/A	ENSP00000473453.1	R4GN21

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1214 AN: 152194 Hom.: 5 Cov.: 31

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

GnomAD2 exomes AF: 0.00708 AC: 1780 AN: 251290 AF XY: 0.00711

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 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.: 31 AF XY: 0.0103 AC XY: 7495 AN XY: 727218

African (AFR) AF: 0.00215 AC: 72 AN: 33480

American (AMR) AF: 0.00771 AC: 345 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 264 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000696 AC: 60 AN: 86256

European-Finnish (FIN) AF: 0.00204 AC: 109 AN: 53366

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.0125 AC: 13936 AN: 1112008

Other (OTH) AF: 0.0111 AC: 669 AN: 60396

GnomAD4 genome AF: 0.00796 AC: 1212 AN: 152312 Hom.: 5 Cov.: 31 AF XY: 0.00750 AC XY: 559 AN XY: 74484

African (AFR) AF: 0.00257 AC: 107 AN: 41574

American (AMR) AF: 0.0118 AC: 180 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 847 AN: 68024

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0104 Hom.: 24

Bravo AF: 0.00849

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0122 AC: 105

ExAC AF: 0.00682 AC: 828

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0128

EpiControl AF: 0.0127

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Schnyder crystalline corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0066	T
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.27
Sift	Benign	0.30	T
Sift4G	Benign	0.70	T
Polyphen		0.064	B
Vest4		0.18
MVP		0.42
MPC		0.57
ClinPred		0.019	T
GERP RS		5.0
PromoterAI		0.012	Neutral
Varity_R		0.22
gMVP		0.31
Mutation Taster		=68/32	polymorphism

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: rs114000606; hg19: chr1-11333812; COSMIC: COSV99060813; COSMIC: COSV99060813;