1-11273222-C-T

Variant names:

• chr1-11273222-C-T
• rs1471509365
• NM_013319.3:c.-310C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BS1_Supporting

The NM_013319.3(UBIAD1):​c.-310C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000804 in 373,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: UBIAD1 NM_013319.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.34
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000901 (2/221984) while in subpopulation EAS AF = 0.000189 (2/10572). AF 95% confidence interval is 0.0000332. There are 0 homozygotes in GnomAdExome4. There are 0 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.-310C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_037451.1	Q9Y5Z9-1
	UBIAD1	NM_013319.3	MANE Select	c.-310C>T		5_prime_UTR	Exon 1 of 2	NP_037451.1	Q9Y5Z9-1
	UBIAD1	NM_001330349.2		c.-310C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001317278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBIAD1	ENST00000376810.6	TSL:1 MANE Select	c.-310C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000366006.5	Q9Y5Z9-1
	UBIAD1	ENST00000376810.6	TSL:1 MANE Select	c.-310C>T		5_prime_UTR	Exon 1 of 2	ENSP00000366006.5	Q9Y5Z9-1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151070 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000901 AC: 2 AN: 221984 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 118666

African (AFR) AF: 0.00 AC: 0 AN: 5210

American (AMR) AF: 0.00 AC: 0 AN: 7696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6198

East Asian (EAS) AF: 0.000189 AC: 2 AN: 10572

South Asian (SAS) AF: 0.00 AC: 0 AN: 33994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 896

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 133172

Other (OTH) AF: 0.00 AC: 0 AN: 12236

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73718

African (AFR) AF: 0.00 AC: 0 AN: 41036

American (AMR) AF: 0.00 AC: 0 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67722

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Schnyder crystalline corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		-1.3
PromoterAI		-0.063	Neutral

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: rs1471509365; hg19: chr1-11333279;