chr1-11273802-G-C

Position:

• chr1-11273802-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_013319.3(UBIAD1):​c.271G>C​(p.Val91Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBIAD1 NM_013319.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

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 5 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity UBIA1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_013319.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.271G>C	p.Val91Leu	missense_variant	1/2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.271G>C	p.Val91Leu	missense_variant	1/3		NP_001317278.1
UBIAD1	NM_001330350.2	c.271G>C	p.Val91Leu	missense_variant	1/2		NP_001317279.1
UBIAD1	XM_047418727.1	c.271G>C	p.Val91Leu	missense_variant	1/3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.271G>C	p.Val91Leu	missense_variant	1/2	1	NM_013319.3	ENSP00000366006	P1
UBIAD1	ENST00000376804.2	c.271G>C	p.Val91Leu	missense_variant	1/2	2		ENSP00000366000

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 10, 2024

The c.271G>C (p.V91L) 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 271, causing the valine (V) at amino acid position 91 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.7	N;N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		0.10	B;.
Vest4		0.69
MutPred		0.66		Loss of catalytic residue at V91 (P = 0.0843);Loss of catalytic residue at V91 (P = 0.0843);
MVP		0.96
MPC		0.62
ClinPred		0.95	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.55
gMVP		0.80

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: rs1651882065; hg19: chr1-11333859;