6-148747575-G-C

Variant names:

• chr6-148747575-G-C
• rs202057866
• NM_005715.3:c.145G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005715.3(UST):​c.145G>C​(p.Gly49Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G49S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UST NM_005715.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.37
• Publications: 0 publications found

Genes affected

UST (HGNC:17223): (uronyl 2-sulfotransferase) Uronyl 2-sulfotransferase transfers sulfate to the 2-position of uronyl residues, such as iduronyl residues in dermatan sulfate and glucuronyl residues in chondroitin sulfate (Kobayashi et al., 1999 [PubMed 10187838]).[supplied by OMIM, Mar 2008]

ENSG00000309666 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005715.3. 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
	UST	NM_005715.3	MANE Select	c.145G>C	p.Gly49Arg	missense	Exon 1 of 8	NP_005706.1	Q9Y2C2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UST	ENST00000367463.5	TSL:1 MANE Select	c.145G>C	p.Gly49Arg	missense	Exon 1 of 8	ENSP00000356433.4	Q9Y2C2
	UST	ENST00000912225.1		c.145G>C	p.Gly49Arg	missense	Exon 1 of 7	ENSP00000582284.1
	UST	ENST00000912224.1		c.145G>C	p.Gly49Arg	missense	Exon 1 of 6	ENSP00000582283.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.012
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		8.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.43	B
Vest4		0.79
MutPred		0.81		Gain of helix (P = 0.0199)
MVP		0.21
MPC		1.1
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.17
gMVP		0.48
Mutation Taster		=71/29	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: rs202057866; hg19: chr6-149068711;