rs118203945

Positions:

• chr1-11273836-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.65

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• 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	UniProt
UBIAD1	NM_013319.3	c.305A>G	p.Asn102Ser	missense_variant	1/2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.305A>G	p.Asn102Ser	missense_variant	1/3		NP_001317278.1
UBIAD1	NM_001330350.2	c.305A>G	p.Asn102Ser	missense_variant	1/2		NP_001317279.1
UBIAD1	XM_047418727.1	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	c.305A>G	p.Asn102Ser	missense_variant	1/2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000376804.2	c.305A>G	p.Asn102Ser	missense_variant	1/2	2		ENSP00000366000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

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.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Pathogenic	0.90	D
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	D
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

Other links and lift over

dbSNP: rs118203945; hg19: chr1-11333893;