chr17-14301571-T-A

Variant names:

• chr17-14301571-T-A
• rs200257944
• NM_006041.3:c.53T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006041.3(HS3ST3B1):​c.53T>A​(p.Leu18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,595,528 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L18P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0033 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (38 hom.)
• Consequence: HS3ST3B1 NM_006041.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.20
• Publications: 1 publications found

Genes affected

HS3ST3B1 (HGNC:5198): (heparan sulfate-glucosamine 3-sulfotransferase 3B1) The protein encoded by this gene is a type II integral membrane protein that belongs to the 3-O-sulfotransferases family. These proteins catalyze the addition of sulfate groups at the 3-OH position of glucosamine in heparan sulfate. The substrate specificity of individual members of the family is based on prior modification of the heparan sulfate chain, thus allowing different members of the family to generate binding sites for different proteins on the same heparan sulfate chain. Following treatment with a histone deacetylase inhibitor, expression of this gene is activated in a pancreatic cell line. The increased expression results in promotion of the epithelial-mesenchymal transition. In addition, the modification catalyzed by this protein allows herpes simplex virus membrane fusion and penetration. A very closely related homolog with an almost identical sulfotransferase domain maps less than 1 Mb away. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040172637).
• BP6: Variant 17-14301571-T-A is Benign according to our data. Variant chr17-14301571-T-A is described in ClinVar as Benign. ClinVar VariationId is 720013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00334 (507/151686) while in subpopulation EAS AF = 0.0229 (117/5106). AF 95% confidence interval is 0.0195. There are 7 homozygotes in GnomAd4. There are 265 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006041.3. 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
	HS3ST3B1	NM_006041.3	MANE Select	c.53T>A	p.Leu18His	missense	Exon 1 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.491T>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.53T>A	p.Leu18His	missense	Exon 1 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.53T>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 508 AN: 151578 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00624

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00193

GnomAD2 exomes AF: 0.00849 AC: 1816 AN: 213858 AF XY: 0.00699

Gnomad AFR exome AF: 0.000510

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0242

Gnomad FIN exome AF: 0.00694

Gnomad NFE exome AF: 0.000993

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00199 AC: 2877 AN: 1443842 Hom.: 38 Cov.: 31 AF XY: 0.00183 AC XY: 1315 AN XY: 718556

African (AFR) AF: 0.000305 AC: 10 AN: 32782

American (AMR) AF: 0.0321 AC: 1416 AN: 44096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.0125 AC: 492 AN: 39326

South Asian (SAS) AF: 0.000152 AC: 13 AN: 85468

European-Finnish (FIN) AF: 0.00701 AC: 290 AN: 41376

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5720

European-Non Finnish (NFE) AF: 0.000428 AC: 475 AN: 1109306

Other (OTH) AF: 0.00297 AC: 178 AN: 59910

GnomAD4 genome AF: 0.00334 AC: 507 AN: 151686 Hom.: 7 Cov.: 33 AF XY: 0.00357 AC XY: 265 AN XY: 74150

African (AFR) AF: 0.000557 AC: 23 AN: 41328

American (AMR) AF: 0.0148 AC: 225 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0229 AC: 117 AN: 5106

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4806

European-Finnish (FIN) AF: 0.00624 AC: 66 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67868

Other (OTH) AF: 0.000954 AC: 2 AN: 2096

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00487

ESP6500AA AF: 0.000539 AC: 2

ESP6500EA AF: 0.000938 AC: 7

ExAC AF: 0.00641 AC: 740

Asia WGS AF: 0.00869 AC: 31 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.081
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.14	T
Polyphen		0.45	P
Vest4		0.39
MVP		0.27
ClinPred		0.042	T
GERP RS		3.0
PromoterAI		-0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.66
Mutation Taster		=96/4	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: rs200257944; hg19: chr17-14204888;