NM_052874.5:c.*3467delC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_052874.5(STX1B):​c.*3467delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 149,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 0 publications found

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]

HSD3B7 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052874.5. 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
	STX1B	NM_052874.5	MANE Select	c.*3467delC		3_prime_UTR	Exon 10 of 10	NP_443106.1	P61266-1
	HSD3B7	NM_025193.4	MANE Select	c.*1171delG		downstream_gene	N/A	NP_079469.2
	HSD3B7	NM_001142777.2		c.*1527delG		downstream_gene	N/A	NP_001136249.1	Q9H2F3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX1B	ENST00000215095.11	TSL:1 MANE Select	c.*3467delC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*3467delC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1
	HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.*1171delG		downstream_gene	N/A	ENSP00000297679.5	Q9H2F3-1

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 20 AN: 149576 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000596

Gnomad OTH AF: 0.00

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.000134 AC: 20 AN: 149694 Hom.: 0 Cov.: 32 AF XY: 0.000151 AC XY: 11 AN XY: 73064

African (AFR) AF: 0.000368 AC: 15 AN: 40812

American (AMR) AF: 0.00 AC: 0 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000596 AC: 4 AN: 67136

Other (OTH) AF: 0.00 AC: 0 AN: 2042

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

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: rs961318568; hg19: chr16-31000674;