rs118203951

Positions:

• chr1-11274042-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP3_Moderate PP5

The NM_013319.3(UBIAD1):​c.511T>C​(p.Ser171Pro) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBIAD1 NM_013319.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.46

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.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity UBIA1_HUMAN there are 7 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, 0.908
• PP5: Variant 1-11274042-T-C is Pathogenic according to our data. Variant chr1-11274042-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 862.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-11274042-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.511T>C	p.Ser171Pro	missense_variant	1/2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.511T>C	p.Ser171Pro	missense_variant	1/3		NP_001317278.1
UBIAD1	NM_001330350.2	c.511T>C	p.Ser171Pro	missense_variant	1/2		NP_001317279.1
UBIAD1	XM_047418727.1	c.511T>C	p.Ser171Pro	missense_variant	1/3		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.511T>C	p.Ser171Pro	missense_variant	1/2	1	NM_013319.3	ENSP00000366006	P1
UBIAD1	ENST00000376804.2	c.511T>C	p.Ser171Pro	missense_variant	1/2	2		ENSP00000366000
UBIAD1	ENST00000483738.1	c.109T>C	p.Ser37Pro	missense_variant	1/3	3		ENSP00000473453
UBIAD1	ENST00000486588.6	c.154T>C	p.Ser52Pro	missense_variant, NMD_transcript_variant	1/5	5		ENSP00000473612

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00152 Hom.: 0

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, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Pathogenic	3.1	M;M;.
MutationTaster	Benign	1.0	A;A
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D;D;.
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.87
MutPred		0.68		Loss of catalytic residue at S171 (P = 0.0108);Loss of catalytic residue at S171 (P = 0.0108);.;
MVP		0.98
MPC		1.6
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.96
gMVP		0.99

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: rs118203951; hg19: chr1-11334099;