Genetic Variant UAP1L1:p.Trp23Gly (chr9-137077599-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207309.3(UAP1L1):c.67T>G(p.Trp23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,358,002 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

UAP1L1
NM_207309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03496641).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3 link	c.67T>G	p.Trp23Gly	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2	Q3KQV9-1
UAP1L1	XM_047424066.1 link	c.67T>G	p.Trp23Gly	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4 link	c.67T>G	p.Trp23Gly	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.67T>G	p.Trp23Gly	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3		Q3KQV9-1
UAP1L1	ENST00000476184.5 link	n.67T>G		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1		A0A087X226

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

242

AN:

149938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000463

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:

0.00

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.000108

AC:

AN:

64934

Hom.:

AF XY:

0.000158

AC XY:

AN XY:

38078

show subpopulations

Gnomad AFR exome

AF:

0.00513

Gnomad AMR exome

AF:

0.000169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000534

GnomAD4 exome

AF:

0.000132

AC:

160

AN:

1207956

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

593754

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.000293

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:

0.00000102

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00165

AC:

248

AN:

150046

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

109

AN XY:

73230

show subpopulations

Gnomad4 AFR

AF:

0.00580

Gnomad4 AMR

AF:

0.000463

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.00164

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.67T>G (p.W23G) alteration is located in exon 1 (coding exon 1) of the UAP1L1 gene. This alteration results from a T to G substitution at nucleotide position 67, causing the tryptophan (W) at amino acid position 23 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

0.20

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-9.8

REVEL

Benign

0.19

Sift

Uncertain

0.011

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.26

MutPred

0.68

Gain of disorder (P = 0.0381);

MVP

0.44

MPC

0.76

ClinPred

0.26

GERP RS

2.5

Varity_R

0.41

gMVP

0.79

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