chr1-11273575-C-T

Position:

• chr1-11273575-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013319.3(UBIAD1):​c.44C>T​(p.Ser15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: UBIAD1 NM_013319.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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=0.09863812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.44C>T	p.Ser15Leu	missense_variant	1/2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.44C>T	p.Ser15Leu	missense_variant	1/3		NP_001317278.1
UBIAD1	NM_001330350.2	c.44C>T	p.Ser15Leu	missense_variant	1/2		NP_001317279.1
UBIAD1	XM_047418727.1	c.44C>T	p.Ser15Leu	missense_variant	1/3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.44C>T	p.Ser15Leu	missense_variant	1/2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000376804.2	c.44C>T	p.Ser15Leu	missense_variant	1/2	2		ENSP00000366000.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 23, 2024

The c.44C>T (p.S15L) alteration is located in exon 1 (coding exon 1) of the UBIAD1 gene. This alteration results from a C to T substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.78	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.099	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.15
Sift	Benign	0.18	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.21		Loss of disorder (P = 0.0381);Loss of disorder (P = 0.0381);
MVP		0.23
MPC		0.46
ClinPred		0.23	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.078
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1364682412; hg19: chr1-11333632;