NM_003944.4:c.1039G>T

Variant names:

• chr1-151365568-C-A
• rs1553204817
• NM_003944.4:c.1039G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_003944.4(SELENBP1):​c.1039G>T​(p.Gly347*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SELENBP1 NM_003944.4 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.21
• Publications: 1 publications found

Genes affected

SELENBP1 (HGNC:10719): (selenium binding protein 1) This gene encodes a member of the selenium-binding protein family. Selenium is an essential nutrient that exhibits potent anticarcinogenic properties, and deficiency of selenium may cause certain neurologic diseases. The effects of selenium in preventing cancer and neurologic diseases may be mediated by selenium-binding proteins, and decreased expression of this gene may be associated with several types of cancer. The encoded protein may play a selenium-dependent role in ubiquitination/deubiquitination-mediated protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

SELENBP1 Gene-Disease associations (from GenCC):

• extraoral halitosis due to methanethiol oxidase deficiency

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
• autosomal recessive extra-oral halitosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-151365568-C-A is Pathogenic according to our data. Variant chr1-151365568-C-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 549495.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003944.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	NM_003944.4	MANE Select	c.1039G>T	p.Gly347*	stop_gained	Exon 9 of 12	NP_003935.2
	SELENBP1	NM_001258289.2		c.1165G>T	p.Gly389*	stop_gained	Exon 9 of 12	NP_001245218.1
	SELENBP1	NM_001258288.2		c.853G>T	p.Gly285*	stop_gained	Exon 8 of 11	NP_001245217.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	ENST00000368868.10	TSL:1 MANE Select	c.1039G>T	p.Gly347*	stop_gained	Exon 9 of 12	ENSP00000357861.5
	SELENBP1	ENST00000426705.6	TSL:2	c.1165G>T	p.Gly389*	stop_gained	Exon 9 of 12	ENSP00000397261.2
	SELENBP1	ENST00000447402.7	TSL:2	c.853G>T	p.Gly285*	stop_gained	Exon 8 of 11	ENSP00000413960.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Extra oral halitosis Pathogenic:1

Apr 16, 2018

SIB Swiss Institute of Bioinformatics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as a Likely Pathogenic, for Extraoral halitosis, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:29255262). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease.

Extraoral halitosis due to methanethiol oxidase deficiency Pathogenic:1

Oct 12, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		7.2
Vest4		0.95
GERP RS		5.2
Mutation Taster		=1/199	disease causing (ClinVar)

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: rs1553204817; hg19: chr1-151338044; COSMIC: COSV64373565; COSMIC: COSV64373565;