NM_001324116.5:c.881G>C

Variant names:

• chr1-162587521-G-C
• rs766124704
• NM_001324116.5:c.881G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001324116.5(UAP1):​c.881G>C​(p.Arg294Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R294Q) 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: 3.33
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1	NM_001324116.5	c.881G>C	p.Arg294Pro	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.881G>C	p.Arg294Pro	missense_variant	Exon 6 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.881G>C	p.Arg294Pro	missense_variant	Exon 6 of 10	1		ENSP00000356903.4
UAP1	ENST00000474728.1	n.76G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;.;D
M_CAP	Benign	0.0092	T
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;M;M;M
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.090	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.99	.;D;.;.
Vest4		0.79
MutPred		0.59		Loss of stability (P = 0.0598);Loss of stability (P = 0.0598);Loss of stability (P = 0.0598);Loss of stability (P = 0.0598);
MVP		0.19
MPC		1.0
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.89
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs766124704; hg19: chr1-162557311;