1-151365649-G-T

Variant names:

• chr1-151365649-G-T
• rs369459403
• NM_003944.4:c.958C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003944.4(SELENBP1):​c.958C>A​(p.Arg320Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R320C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 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: ClinGen, 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

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.958C>A	p.Arg320Ser	missense	Exon 9 of 12	NP_003935.2
	SELENBP1	NM_001258289.2		c.1084C>A	p.Arg362Ser	missense	Exon 9 of 12	NP_001245218.1	Q13228-4
	SELENBP1	NM_001258288.2		c.772C>A	p.Arg258Ser	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.958C>A	p.Arg320Ser	missense	Exon 9 of 12	ENSP00000357861.5	Q13228-1
	SELENBP1	ENST00000426705.6	TSL:2	c.1084C>A	p.Arg362Ser	missense	Exon 9 of 12	ENSP00000397261.2	Q13228-4
	SELENBP1	ENST00000896531.1		c.1048C>A	p.Arg350Ser	missense	Exon 10 of 13	ENSP00000566590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.83
MutPred		0.92		Loss of stability (P = 0.0474)
MVP		0.42
MPC		0.45
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.86
gMVP		0.76
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs369459403; hg19: chr1-151338125;