chr1-162581388-A-T

Variant names:

• chr1-162581388-A-T
• rs753571677
• NM_001324116.5:c.763A>T

Variant summary

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

The NM_001324116.5(UAP1):​c.763A>T​(p.Ile255Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I255V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UAP1 NM_001324116.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39
• Publications: 0 publications found

Genes affected

UAP1 (HGNC:12457): (UDP-N-acetylglucosamine pyrophosphorylase 1) Enables identical protein binding activity. Predicted to be involved in UDP-N-acetylglucosamine biosynthetic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1	NM_001324116.5	c.763A>T	p.Ile255Leu	missense_variant	Exon 5 of 11	ENST00000367925.6	NP_001311045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1	ENST00000367925.6	c.763A>T	p.Ile255Leu	missense_variant	Exon 5 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.763A>T	p.Ile255Leu	missense_variant	Exon 5 of 10	1		ENSP00000356903.4
UAP1	ENST00000474728.1	n.-43A>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PhyloP100		7.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.12	.;B;.;.
Vest4		0.59
MutPred		0.73		Loss of methylation at K258 (P = 0.0585);Loss of methylation at K258 (P = 0.0585);Loss of methylation at K258 (P = 0.0585);Loss of methylation at K258 (P = 0.0585);
MVP		0.082
MPC		0.83
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.52
Mutation Taster		=45/55	disease causing

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: rs753571677; hg19: chr1-162551178;