Genetic Variant UAP1L1:p.Phe186Leu (chr9-137078565-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207309.3(UAP1L1):c.558C>A(p.Phe186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

UAP1L1
NM_207309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.229

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 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
UAP1L1	NM_207309.3 link	c.558C>A	p.Phe186Leu	missense_variant	Exon 3 of 9	ENST00000409858.8	NP_997192.2	Q3KQV9-1
UAP1L1	XM_047424066.1 link	c.786C>A	p.Phe262Leu	missense_variant	Exon 2 of 8		XP_047280022.1
UAP1L1	XM_006717317.4 link	c.558C>A	p.Phe186Leu	missense_variant	Exon 3 of 8		XP_006717380.1
UAP1L1	XM_011519182.3 link	c.57C>A	p.Phe19Leu	missense_variant	Exon 2 of 7		XP_011517484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1L1	ENST00000409858.8 link	c.558C>A	p.Phe186Leu	missense_variant	Exon 3 of 9	1	NM_207309.3	ENSP00000386935.3		Q3KQV9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250414

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000193

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

Mar 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.558C>A (p.F186L) alteration is located in exon 3 (coding exon 3) of the UAP1L1 gene. This alteration results from a C to A substitution at nucleotide position 558, causing the phenylalanine (F) at amino acid position 186 to be replaced by a leucine (L). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.3

M;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;P

Vest4

0.55

MutPred

0.77

Gain of helix (P = 0.2684);.;

MVP

0.39

MPC

0.60

ClinPred

0.94

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.74

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