Genetic Variant NM_001324116.5:c.15C>A (chr1-162566083-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001324116.5(UAP1):c.15C>A(p.Asp5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UAP1
NM_001324116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.225

Publications

0 publications found

Variant links:

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]

UAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052416354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1	NM_001324116.5 link	c.15C>A	p.Asp5Glu	missense_variant	Exon 2 of 11	ENST00000367925.6	NP_001311045.1	Q16222-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1	ENST00000367925.6 link	c.15C>A	p.Asp5Glu	missense_variant	Exon 2 of 11	5	NM_001324116.5	ENSP00000356902.1		Q16222-1
UAP1	ENST00000367926.9 link	c.15C>A	p.Asp5Glu	missense_variant	Exon 2 of 10	1		ENSP00000356903.4		Q16222-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111900

Other (OTH)

AF:

0.0000498

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.15C>A (p.D5E) alteration is located in exon 2 (coding exon 1) of the UAP1 gene. This alteration results from a C to A substitution at nucleotide position 15, causing the aspartic acid (D) at amino acid position 5 to be replaced by a glutamic acid (E). 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

0.086

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;.;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.72

T;T;.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.052

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N;N;N

PhyloP100

-0.23

PrimateAI

Benign

0.41

PROVEAN

Benign

0.27

N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.053

MutPred

0.23

Gain of disorder (P = 0.1536);Gain of disorder (P = 0.1536);Gain of disorder (P = 0.1536);Gain of disorder (P = 0.1536);

MVP

0.10

MPC

0.36

ClinPred

0.064

GERP RS

0.30

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.061

gMVP

0.14

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

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NM_001324116.5:c.15C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over