chr6-148949693-G-A

Variant names:

• chr6-148949693-G-A
• rs13219957
• NM_005715.3:c.448-4179G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005715.3(UST):​c.448-4179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,130 control chromosomes in the GnomAD database, including 1,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1415 hom., cov: 31)
• Consequence: UST NM_005715.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UST	NM_005715.3	c.448-4179G>A		intron_variant	Intron 3 of 7	ENST00000367463.5	NP_005706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UST	ENST00000367463.5	c.448-4179G>A		intron_variant	Intron 3 of 7	1	NM_005715.3	ENSP00000356433.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19181 AN: 152012 Hom.: 1417 Cov.: 31

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19191 AN: 152130 Hom.: 1415 Cov.: 31 AF XY: 0.125 AC XY: 9295 AN XY: 74364

African (AFR) AF: 0.0514 AC: 2132 AN: 41510

American (AMR) AF: 0.180 AC: 2745 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3472

East Asian (EAS) AF: 0.111 AC: 575 AN: 5178

South Asian (SAS) AF: 0.115 AC: 554 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1495 AN: 10560

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10759 AN: 67990

Other (OTH) AF: 0.130 AC: 274 AN: 2114

Alfa AF: 0.147 Hom.: 3373

Bravo AF: 0.128

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.58
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs13219957; hg19: chr6-149270829;