9-137078083-T-C

Variant names:

• chr9-137078083-T-C
• rs1330464776
• NM_207309.3:c.323T>C

Variant summary

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

The NM_207309.3(UAP1L1):​c.323T>C​(p.Val108Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,397,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.323T>C	p.Val108Ala	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.323T>C	p.Val108Ala	missense	Exon 2 of 9	ENSP00000386935.3	Q3KQV9-1
	UAP1L1	ENST00000907215.1		c.323T>C	p.Val108Ala	missense	Exon 2 of 9	ENSP00000577274.1
	UAP1L1	ENST00000915583.1		c.323T>C	p.Val108Ala	missense	Exon 2 of 9	ENSP00000585642.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000648 AC: 1 AN: 154336 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

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: 7.15e-7 AC: 1 AN: 1397826 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689446

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.0000280 AC: 1 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078870

Other (OTH) AF: 0.00 AC: 0 AN: 57972

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Benign	0.049	D
Sift4G	Benign	0.076	T
Polyphen		0.99	D
Vest4		0.49
MutPred		0.77		Loss of catalytic residue at V108 (P = 0.0407)
MVP		0.33
MPC		0.39
ClinPred		0.69	D
GERP RS		5.0
PromoterAI		0.15	Neutral
Varity_R		0.24
gMVP		0.70
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1330464776; hg19: chr9-139972535;