chr1-162587514-G-A

Variant names:

• chr1-162587514-G-A
• NM_001324116.5:c.874G>A

Variant summary

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

The NM_001324116.5(UAP1):​c.874G>A​(p.Val292Ile) 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: 9.46
• 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.874G>A	p.Val292Ile	missense_variant	Exon 6 of 11	ENST00000367925.6	NP_001311045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1	ENST00000367925.6	c.874G>A	p.Val292Ile	missense_variant	Exon 6 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.874G>A	p.Val292Ile	missense_variant	Exon 6 of 10	1		ENSP00000356903.4
UAP1	ENST00000474728.1	n.69G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.874G>A (p.V292I) alteration is located in exon 6 (coding exon 5) of the UAP1 gene. This alteration results from a G to A substitution at nucleotide position 874, causing the valine (V) at amino acid position 292 to be replaced by an isoleucine (I). 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	0.094
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;.;D
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	L;L;L;L
PhyloP100		9.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.98	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.038	D;D;D;D
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.96	.;D;.;.
Vest4		0.63
MutPred		0.43		Loss of disorder (P = 0.2604);Loss of disorder (P = 0.2604);Loss of disorder (P = 0.2604);Loss of disorder (P = 0.2604);
MVP		0.16
MPC		0.98
ClinPred		0.88	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.38
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-162557304;