chr1-162576896-A-C

Variant names:

• chr1-162576896-A-C
• rs1654219765
• NM_001324116.5:c.400A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001324116.5(UAP1):​c.400A>C​(p.Thr134Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: UAP1 NM_001324116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1	NM_001324116.5	c.400A>C	p.Thr134Pro	missense_variant	Exon 3 of 11	ENST00000367925.6	NP_001311045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1	ENST00000367925.6	c.400A>C	p.Thr134Pro	missense_variant	Exon 3 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.400A>C	p.Thr134Pro	missense_variant	Exon 3 of 10	1		ENSP00000356903.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.400A>C (p.T134P) alteration is located in exon 3 (coding exon 2) of the UAP1 gene. This alteration results from a A to C substitution at nucleotide position 400, causing the threonine (T) at amino acid position 134 to be replaced by a proline (P). 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	0.16
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PhyloP100		7.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.9	D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.046	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.73
MutPred		0.89		Loss of phosphorylation at T134 (P = 0.0474);Loss of phosphorylation at T134 (P = 0.0474);Loss of phosphorylation at T134 (P = 0.0474);Loss of phosphorylation at T134 (P = 0.0474);
MVP		0.33
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.96
gMVP		0.86
Mutation Taster		=35/65	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: rs1654219765; hg19: chr1-162546686;