1-162566298-T-C

Variant names:

• chr1-162566298-T-C
• rs1191060148
• NM_001324116.5:c.230T>C

Variant summary

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

The NM_001324116.5(UAP1):​c.230T>C​(p.Leu77Ser) variant causes a missense change. 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: 6.07
• 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 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.230T>C	p.Leu77Ser	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.230T>C	p.Leu77Ser	missense_variant	Exon 2 of 11	5	NM_001324116.5	ENSP00000356902.1
UAP1	ENST00000367926.9	c.230T>C	p.Leu77Ser	missense_variant	Exon 2 of 10	1		ENSP00000356903.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230T>C (p.L77S) alteration is located in exon 2 (coding exon 1) of the UAP1 gene. This alteration results from a T to C substitution at nucleotide position 230, causing the leucine (L) at amino acid position 77 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;.;D
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PhyloP100		6.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D;N;D;D
REVEL	Uncertain	0.31
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.79	.;P;.;.
Vest4		0.66
MutPred		0.55		Gain of glycosylation at L77 (P = 0.0047);Gain of glycosylation at L77 (P = 0.0047);Gain of glycosylation at L77 (P = 0.0047);Gain of glycosylation at L77 (P = 0.0047);
MVP		0.15
MPC		1.4
ClinPred		0.97	D
GERP RS		5.2
PromoterAI		0.020	Neutral
Varity_R		0.47
gMVP		0.78
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: rs1191060148; hg19: chr1-162536088;