NM_013319.3:c.132G>C

Variant names:

• chr1-11273663-G-C
• rs1651873245
• NM_013319.3:c.132G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013319.3(UBIAD1):​c.132G>C​(p.Gln44His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UBIAD1 NM_013319.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.273
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09097606).

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.132G>C	p.Gln44His	missense	Exon 1 of 2	NP_037451.1	Q9Y5Z9-1
	UBIAD1	NM_001330349.2		c.132G>C	p.Gln44His	missense	Exon 1 of 3	NP_001317278.1
	UBIAD1	NM_001330350.2		c.132G>C	p.Gln44His	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.132G>C	p.Gln44His	missense	Exon 1 of 2	ENSP00000366006.5	Q9Y5Z9-1
	UBIAD1	ENST00000376804.2	TSL:2	c.132G>C	p.Gln44His	missense	Exon 1 of 2	ENSP00000366000.1	Q9Y5Z9-2
	UBIAD1	ENST00000486588.6	TSL:5	n.-226G>C		upstream_gene	N/A	ENSP00000473612.1	R4GNE3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.76
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.27
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Benign	0.56	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.36		Loss of stability (P = 0.0973)
MVP		0.15
MPC		0.49
ClinPred		0.035	T
GERP RS		-6.6
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.062
gMVP		0.18
Mutation Taster		=88/12	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: rs1651873245; hg19: chr1-11333720; COSMIC: COSV105311108; COSMIC: COSV105311108;