dbSNP rs567890644: UAP1L1:p.Pro75Ala (chr9-137077755-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207309.3(UAP1L1):c.223C>G(p.Pro75Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UAP1L1
NM_207309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

UAP1L1 (HGNC:28082): (UDP-N-acetylglucosamine pyrophosphorylase 1 like 1) Predicted to enable UDP-N-acetylglucosamine diphosphorylase activity. Predicted to be involved in UDP-N-acetylglucosamine biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

UAP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21546668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3 link	c.223C>G	p.Pro75Ala	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2	Q3KQV9-1
UAP1L1	XM_047424066.1 link	c.223C>G	p.Pro75Ala	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4 link	c.223C>G	p.Pro75Ala	missense_variant	Exon 1 of 8		XP_006717380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1L1	ENST00000409858.8 link	c.223C>G	p.Pro75Ala	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3		Q3KQV9-1
UAP1L1	ENST00000476184.5 link	n.223C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1		A0A087X226

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1091246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

518446

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150846

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73618

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.223C>G (p.P75A) alteration is located in exon 1 (coding exon 1) of the UAP1L1 gene. This alteration results from a C to G substitution at nucleotide position 223, causing the proline (P) at amino acid position 75 to be replaced by an alanine (A). 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

0.070

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.15

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.52

M_CAP

Benign

0.060

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.12

Sift

Benign

0.045

Sift4G

Uncertain

0.038

Polyphen

0.74

Vest4

0.15

MutPred

0.60

Loss of catalytic residue at P75 (P = 0.004);

MVP

0.24

MPC

0.24

ClinPred

0.57

GERP RS

0.73

Varity_R

0.12

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over