9-137077761-G-C

Variant names:

• chr9-137077761-G-C
• rs1401743196
• NM_207309.3:c.229G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207309.3(UAP1L1):​c.229G>C​(p.Glu77Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000663 in 150,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UAP1L1 NM_207309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15335432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3	c.229G>C	p.Glu77Gln	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2
UAP1L1	XM_047424066.1	c.229G>C	p.Glu77Gln	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4	c.229G>C	p.Glu77Gln	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.229G>C	p.Glu77Gln	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3
UAP1L1	ENST00000476184.5	n.229G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150858 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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150858 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73668

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.078
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.17	B
Vest4		0.057
MutPred		0.50		Gain of MoRF binding (P = 0.0228);
MVP		0.055
MPC		0.25
ClinPred		0.20	T
GERP RS		0.64
Varity_R		0.077
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs1401743196; hg19: chr9-139972213;