1-162581442-G-T

Variant names:

• chr1-162581442-G-T
• rs756522769
• NM_001324116.5:c.817G>T

Variant summary

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

The NM_001324116.5(UAP1):​c.817G>T​(p.Ala273Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UAP1 NM_001324116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.86
• 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.817G>T	p.Ala273Ser	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.817G>T	p.Ala273Ser	missense_variant	Exon 5 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.817G>T	p.Ala273Ser	missense_variant	Exon 5 of 10	1		ENSP00000356903.4
UAP1	ENST00000474728.1	n.12G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.817G>T (p.A273S) alteration is located in exon 5 (coding exon 4) of the UAP1 gene. This alteration results from a G to T substitution at nucleotide position 817, causing the alanine (A) at amino acid position 273 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;T;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M;M
PhyloP100		9.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.63
MutPred		0.72		Gain of ubiquitination at K271 (P = 0.0683);Gain of ubiquitination at K271 (P = 0.0683);Gain of ubiquitination at K271 (P = 0.0683);Gain of ubiquitination at K271 (P = 0.0683);
MVP		0.15
MPC		1.1
ClinPred		0.94	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.70
Mutation Taster		=62/38	polymorphism

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: rs756522769; hg19: chr1-162551232;