chr9-137077696-A-G

Variant names:

• chr9-137077696-A-G
• rs1476426643
• NM_207309.3:c.164A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207309.3(UAP1L1):​c.164A>G​(p.Glu55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,143,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E55A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08034471).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207309.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UAP1L1	NM_207309.3	MANE Select	c.164A>G	p.Glu55Gly	missense	Exon 1 of 9	NP_997192.2	Q3KQV9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UAP1L1	ENST00000409858.8	TSL:1 MANE Select	c.164A>G	p.Glu55Gly	missense	Exon 1 of 9	ENSP00000386935.3	Q3KQV9-1
	UAP1L1	ENST00000907215.1		c.164A>G	p.Glu55Gly	missense	Exon 1 of 9	ENSP00000577274.1
	UAP1L1	ENST00000915583.1		c.164A>G	p.Glu55Gly	missense	Exon 1 of 9	ENSP00000585642.1

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148414 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 10 AN: 995060 Hom.: 0 Cov.: 31 AF XY: 0.00000426 AC XY: 2 AN XY: 469078

African (AFR) AF: 0.00 AC: 0 AN: 19930

American (AMR) AF: 0.00 AC: 0 AN: 5622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10398

East Asian (EAS) AF: 0.00 AC: 0 AN: 18252

South Asian (SAS) AF: 0.00 AC: 0 AN: 19058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2446

European-Non Finnish (NFE) AF: 0.0000115 AC: 10 AN: 865934

Other (OTH) AF: 0.00 AC: 0 AN: 37346

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148414 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72312

African (AFR) AF: 0.00 AC: 0 AN: 40922

American (AMR) AF: 0.00 AC: 0 AN: 14948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66630

Other (OTH) AF: 0.00 AC: 0 AN: 2042

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.86	L
PhyloP100		-0.47
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.034
Sift	Benign	0.35	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.59		Loss of solvent accessibility (P = 0.0224)
MVP		0.048
MPC		0.29
ClinPred		0.045	T
GERP RS		-0.21
PromoterAI		-0.19	Neutral
Varity_R		0.055
gMVP		0.54
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1476426643; hg19: chr9-139972148;