9-137078214-C-G

Variant names:

• chr9-137078214-C-G
• rs1325192512
• NM_207309.3:c.454C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207309.3(UAP1L1):​c.454C>G​(p.Leu152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

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]

ACMG classification

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=0.31233013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3	c.454C>G	p.Leu152Val	missense_variant	Exon 2 of 9	ENST00000409858.8	NP_997192.2
UAP1L1	XM_047424066.1	c.682C>G	p.Leu228Val	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4	c.454C>G	p.Leu152Val	missense_variant	Exon 2 of 8		XP_006717380.1
UAP1L1	XM_011519182.3	c.-80C>G		5_prime_UTR_variant	Exon 1 of 7		XP_011517484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1L1	ENST00000409858.8	c.454C>G	p.Leu152Val	missense_variant	Exon 2 of 9	1	NM_207309.3	ENSP00000386935.3
UAP1L1	ENST00000360271	c.-163C>G		5_prime_UTR_variant	Exon 1 of 7	2		ENSP00000353409.3
UAP1L1	ENST00000476184.5	n.290-288C>G		intron_variant	Intron 1 of 2	3		ENSP00000484649.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395562 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 688342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454C>G (p.L152V) alteration is located in exon 2 (coding exon 2) of the UAP1L1 gene. This alteration results from a C to G substitution at nucleotide position 454, causing the leucine (L) at amino acid position 152 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.091	T
Sift4G	Uncertain	0.038	D
Polyphen		0.81	P
Vest4		0.47
MutPred		0.48		Gain of MoRF binding (P = 0.0904);
MVP		0.55
MPC		0.83
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1325192512; hg19: chr9-139972666;