Genetic Variant UAP1L1:p.Ala53Gly (chr9-137077690-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207309.3(UAP1L1):c.158C>G(p.Ala53Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 2.71

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3402565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3 link	c.158C>G	p.Ala53Gly	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2	Q3KQV9-1
UAP1L1	XM_047424066.1 link	c.158C>G	p.Ala53Gly	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4 link	c.158C>G	p.Ala53Gly	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.158C>G	p.Ala53Gly	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3		Q3KQV9-1
UAP1L1	ENST00000476184.5 link	n.158C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1		A0A087X226

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

993572

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

469196

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158C>G (p.A53G) 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 158, causing the alanine (A) at amino acid position 53 to be replaced by a glycine (G). 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

0.21

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.3

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.97

Vest4

0.17

MutPred

0.62

Gain of methylation at R52 (P = 0.0657);

MVP

0.39

MPC

0.87

ClinPred

0.96

GERP RS

3.3

Varity_R

0.43

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over