rs1325192512

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-137078214-C-G
• chr9-137078214-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31233013).

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.454C>G	p.Leu152Val	missense	Exon 2 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.454C>G	p.Leu152Val	missense	Exon 2 of 9	ENSP00000386935.3	Q3KQV9-1
	UAP1L1	ENST00000907215.1		c.454C>G	p.Leu152Val	missense	Exon 2 of 9	ENSP00000577274.1
	UAP1L1	ENST00000915583.1		c.454C>G	p.Leu152Val	missense	Exon 2 of 9	ENSP00000585642.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078522

Other (OTH) AF: 0.0000173 AC: 1 AN: 57912

GnomAD4 genome Cov.: 33

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	0.12
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
PhyloP100		2.3
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
PromoterAI		-0.061	Neutral
Varity_R		0.24
gMVP		0.71
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs1325192512; hg19: chr9-139972666;