9-137078220-G-A

Variant names:

• chr9-137078220-G-A
• rs759763823
• NM_207309.3:c.460G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_207309.3(UAP1L1):​c.460G>A​(p.Gly154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,547,398 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (9 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.03

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072662532).
• BP6: Variant 9-137078220-G-A is Benign according to our data. Variant chr9-137078220-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2659799.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3	c.460G>A	p.Gly154Ser	missense_variant	Exon 2 of 9	ENST00000409858.8	NP_997192.2
UAP1L1	XM_047424066.1	c.688G>A	p.Gly230Ser	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4	c.460G>A	p.Gly154Ser	missense_variant	Exon 2 of 8		XP_006717380.1
UAP1L1	XM_011519182.3	c.-74G>A		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.460G>A	p.Gly154Ser	missense_variant	Exon 2 of 9	1	NM_207309.3	ENSP00000386935.3
UAP1L1	ENST00000360271	c.-157G>A		5_prime_UTR_variant	Exon 1 of 7	2		ENSP00000353409.3
UAP1L1	ENST00000476184.5	n.290-282G>A		intron_variant	Intron 1 of 2	3		ENSP00000484649.1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00127 AC: 184 AN: 144748 Hom.: 0 AF XY: 0.00113 AC XY: 88 AN XY: 77954

Gnomad AFR exome AF: 0.000281

Gnomad AMR exome AF: 0.00209

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.00216

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00202 AC: 2817 AN: 1395070 Hom.: 9 Cov.: 32 AF XY: 0.00202 AC XY: 1391 AN XY: 688116

Gnomad4 AFR exome AF: 0.0000950

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.000159

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000195

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152328 Hom.: 0 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74488

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.00176

ExAC AF: 0.000116 AC: 4

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.460G>A (p.G154S) alteration is located in exon 2 (coding exon 2) of the UAP1L1 gene. This alteration results from a G to A substitution at nucleotide position 460, causing the glycine (G) at amino acid position 154 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UAP1L1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.011
Sift	Benign	0.55	T
Sift4G	Benign	0.51	T
Polyphen		0.10	B
Vest4		0.097
MVP		0.030
MPC		0.29
ClinPred		0.0058	T
GERP RS		3.1
Varity_R		0.071
gMVP		0.56

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: rs759763823; hg19: chr9-139972672;