9-137077715-C-A

Variant names:

• chr9-137077715-C-A
• NM_207309.3:c.183C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207309.3(UAP1L1):​c.183C>A​(p.His61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000099 in 1,009,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039275765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3	c.183C>A	p.His61Gln	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2
UAP1L1	XM_047424066.1	c.183C>A	p.His61Gln	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4	c.183C>A	p.His61Gln	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	c.183C>A	p.His61Gln	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3
UAP1L1	ENST00000476184.5	n.183C>A		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.90e-7 AC: 1 AN: 1009702 Hom.: 0 Cov.: 31 AF XY: 0.00000210 AC XY: 1 AN XY: 475560

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: 0.00000114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.183C>A (p.H61Q) alteration is located in exon 1 (coding exon 1) of the UAP1L1 gene. This alteration results from a C to A substitution at nucleotide position 183, causing the histidine (H) at amino acid position 61 to be replaced by a glutamine (Q). 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	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.0
DANN	Benign	0.78
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.68	N
REVEL	Benign	0.0080
Sift	Benign	0.61	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.26		Loss of methylation at R59 (P = 0.0491);
MVP		0.014
MPC		0.24
ClinPred		0.036	T
GERP RS		-3.4
Varity_R		0.040
gMVP		0.41

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.

Other links and lift over

hg19: chr9-139972167;