rs1388558593

Variant names:

• chr9-137077759-C-G
• rs1388558593
• NM_207309.3:c.227C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207309.3(UAP1L1):​c.227C>G​(p.Pro76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,261,656 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011665523).

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.227C>G	p.Pro76Arg	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.227C>G	p.Pro76Arg	missense	Exon 1 of 9	ENSP00000386935.3	Q3KQV9-1
	UAP1L1	ENST00000907215.1		c.227C>G	p.Pro76Arg	missense	Exon 1 of 9	ENSP00000577274.1
	UAP1L1	ENST00000915583.1		c.227C>G	p.Pro76Arg	missense	Exon 1 of 9	ENSP00000585642.1

Frequencies

GnomAD3 genomes AF: 0.0000464 AC: 7 AN: 150980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000461

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00193 AC: 2 AN: 1034 AF XY: 0.00157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00389

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000990 AC: 11 AN: 1110676 Hom.: 0 Cov.: 31 AF XY: 0.00000944 AC XY: 5 AN XY: 529424

African (AFR) AF: 0.00 AC: 0 AN: 22730

American (AMR) AF: 0.000972 AC: 9 AN: 9256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14542

East Asian (EAS) AF: 0.00 AC: 0 AN: 25892

South Asian (SAS) AF: 0.00 AC: 0 AN: 31512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2956

European-Non Finnish (NFE) AF: 0.00000214 AC: 2 AN: 936630

Other (OTH) AF: 0.00 AC: 0 AN: 44496

GnomAD4 genome AF: 0.0000464 AC: 7 AN: 150980 Hom.: 0 Cov.: 32 AF XY: 0.0000678 AC XY: 5 AN XY: 73702

African (AFR) AF: 0.00 AC: 0 AN: 41270

American (AMR) AF: 0.000461 AC: 7 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10128

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67652

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.54
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Benign	0.64	T
Sift4G	Benign	0.43	T
Polyphen		0.0050	B
Vest4		0.062
MutPred		0.57		Gain of MoRF binding (P = 0.0026)
MVP		0.10
MPC		0.26
ClinPred		0.036	T
GERP RS		3.7
PromoterAI		-0.0086	Neutral
Varity_R		0.15
gMVP		0.61
Mutation Taster		=82/18	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: rs1388558593; hg19: chr9-139972211;