1-162566289-G-C

Variant names:

• chr1-162566289-G-C
• rs770874357
• NM_001324116.5:c.221G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001324116.5(UAP1):​c.221G>C​(p.Arg74Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. R74L) 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: 4.64
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36474454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1	NM_001324116.5	c.221G>C	p.Arg74Pro	missense_variant	Exon 2 of 11	ENST00000367925.6	NP_001311045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1	ENST00000367925.6	c.221G>C	p.Arg74Pro	missense_variant	Exon 2 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.221G>C	p.Arg74Pro	missense_variant	Exon 2 of 10	1		ENSP00000356903.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251316 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.00086
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N;N;N;N
PhyloP100		4.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.5	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.88	T;T;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.68
MutPred		0.51		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.36
MPC		1.4
ClinPred		0.79	D
GERP RS		5.3
PromoterAI		-0.021	Neutral
Varity_R		0.62
gMVP		0.80
Mutation Taster		=37/63	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: rs770874357; hg19: chr1-162536079;