16-30989353-A-AG

Variant names:

• chr16-30989353-A-AG
• rs961318568
• NM_052874.5:c.*3467dupC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_052874.5(STX1B):​c.*3467dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 149,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.450

Genes affected

STX1B (HGNC:18539): (syntaxin 1B) The protein encoded by this gene belongs to a family of proteins thought to play a role in the exocytosis of synaptic vesicles. Vesicle exocytosis releases vesicular contents and is important to various cellular functions. For instance, the secretion of transmitters from neurons plays an important role in synaptic transmission. After exocytosis, the membrane and proteins from the vesicle are retrieved from the plasma membrane through the process of endocytosis. Mutations in this gene have been identified as one cause of fever-associated epilepsy syndromes. A possible link between this gene and Parkinson's disease has also been suggested. [provided by RefSeq, Jan 2015]

HSD3B7 (HGNC:18324): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7) This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 232 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1B	NM_052874.5	c.*3467dupC		3_prime_UTR_variant	Exon 10 of 10	ENST00000215095.11	NP_443106.1
HSD3B7	NM_025193.4	c.*1170_*1171insG		downstream_gene_variant		ENST00000297679.10	NP_079469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095	c.*3467dupC		3_prime_UTR_variant	Exon 10 of 10	1	NM_052874.5	ENSP00000215095.5
HSD3B7	ENST00000297679.10	c.*1170_*1171insG		downstream_gene_variant		1	NM_025193.4	ENSP00000297679.5
HSD3B7	ENST00000262520.10	c.*1526_*1527insG		downstream_gene_variant		2		ENSP00000262520.6

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 232 AN: 149576 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000399

Gnomad ASJ AF: 0.0108

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00255

Gnomad FIN AF: 0.0000970

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.00198

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 60 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00155 AC: 232 AN: 149694 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 98 AN XY: 73064

Gnomad4 AFR AF: 0.000564

Gnomad4 AMR AF: 0.000399

Gnomad4 ASJ AF: 0.0108

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.00255

Gnomad4 FIN AF: 0.0000970

Gnomad4 NFE AF: 0.00220

Gnomad4 OTH AF: 0.00196

Bravo AF: 0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal hemochromatosis Uncertain:1

Mar 23, 2023

Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs961318568; hg19: chr16-31000674;