rs748871803

Variant names:

• chr1-151365570-G-A
• rs748871803
• NM_003944.4:c.1037C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151365570-G-A
• chr1-151365570-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003944.4(SELENBP1):​c.1037C>T​(p.Thr346Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T346R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• 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: STRONG, MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia, Ambry Genetics
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3097931).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	NM_003944.4	MANE Select	c.1037C>T	p.Thr346Ile	missense	Exon 9 of 12	NP_003935.2
	SELENBP1	NM_001258289.2		c.1163C>T	p.Thr388Ile	missense	Exon 9 of 12	NP_001245218.1	Q13228-4
	SELENBP1	NM_001258288.2		c.851C>T	p.Thr284Ile	missense	Exon 8 of 11	NP_001245217.1	Q13228-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	ENST00000368868.10	TSL:1 MANE Select	c.1037C>T	p.Thr346Ile	missense	Exon 9 of 12	ENSP00000357861.5	Q13228-1
	SELENBP1	ENST00000426705.6	TSL:2	c.1163C>T	p.Thr388Ile	missense	Exon 9 of 12	ENSP00000397261.2	Q13228-4
	SELENBP1	ENST00000896531.1		c.1127C>T	p.Thr376Ile	missense	Exon 10 of 13	ENSP00000566590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251250 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.069	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.068
Sift	Benign	0.038	D
Sift4G	Benign	0.071	T
Polyphen		0.014	B
Vest4		0.42
MutPred		0.60		Loss of disorder (P = 0.0687)
MVP		0.092
MPC		0.099
ClinPred		0.17	T
GERP RS		0.13
Varity_R		0.053
gMVP		0.25
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs748871803; hg19: chr1-151338046;