1-11273663-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 3		NP_001317278.1
UBIAD1	NM_001330350.2	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 2		NP_001317279.1
UBIAD1	XM_047418727.1	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000376804.2	c.132G>C	p.Gln44His	missense_variant	Exon 1 of 2	2		ENSP00000366000.1
UBIAD1	ENST00000486588.6	n.-226G>C		upstream_gene_variant		5		ENSP00000473612.1

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

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: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.132G>C (p.Q44H) alteration is located in exon 1 (coding exon 1) of the UBIAD1 gene. This alteration results from a G to C substitution at nucleotide position 132, causing the glutamine (Q) at amino acid position 44 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.20
Sift	Benign	0.56	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.0	B;.
Vest4		0.090
MutPred		0.36		Loss of stability (P = 0.0973);Loss of stability (P = 0.0973);
MVP		0.15
MPC		0.49
ClinPred		0.035	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.062
gMVP		0.18

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: rs1651873245; hg19: chr1-11333720; COSMIC: COSV105311108; COSMIC: COSV105311108;