chr17-14301571-T-A

Position:

• chr17-14301571-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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, single submitter B:1
• Conservation: PhyloP100: 3.20

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

Verdict is Benign. Variant got -14 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 id is 720013.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3B1	NM_006041.3	c.53T>A	p.Leu18His	missense_variant	1/2	ENST00000360954.3
HS3ST3B1	NR_130138.2	n.491T>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3B1	ENST00000360954.3	c.53T>A	p.Leu18His	missense_variant	1/2	1	NM_006041.3	P1
HS3ST3B1	ENST00000466596.5	c.53T>A	p.Leu18His	missense_variant, NMD_transcript_variant	1/3	2

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

GnomAD3 exomes AF: 0.00849 AC: 1816 AN: 213858 Hom.: 30 AF XY: 0.00699 AC XY: 837 AN XY: 119730

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 SAS exome AF: 0.000102

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

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.0321

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00701

Gnomad4 NFE exome AF: 0.000428

Gnomad4 OTH exome AF: 0.00297

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

Gnomad4 AFR AF: 0.000557

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0229

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.00624

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.000954

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.66

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: rs200257944; hg19: chr17-14204888;