1-151364639-G-C

Variant names:

• chr1-151364639-G-C
• rs1363033403
• NM_003944.4:c.1323C>G

Variant summary

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

The NM_003944.4(SELENBP1):​c.1323C>G​(p.Asn441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,216 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

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]

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=0.40563914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENBP1	NM_003944.4	c.1323C>G	p.Asn441Lys	missense_variant	Exon 12 of 12	ENST00000368868.10	NP_003935.2
SELENBP1	NM_001258289.2	c.1449C>G	p.Asn483Lys	missense_variant	Exon 12 of 12		NP_001245218.1
SELENBP1	NM_001258288.2	c.1137C>G	p.Asn379Lys	missense_variant	Exon 11 of 11		NP_001245217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENBP1	ENST00000368868.10	c.1323C>G	p.Asn441Lys	missense_variant	Exon 12 of 12	1	NM_003944.4	ENSP00000357861.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461016 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726790

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33466

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44614

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26036

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39688

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86144

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53396

Gnomad4 NFE exome AF: 0.00000270 AC: 3 AN: 1111558

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000146968 AN: 0.0000146968

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1323C>G (p.N441K) alteration is located in exon 12 (coding exon 12) of the SELENBP1 gene. This alteration results from a C to G substitution at nucleotide position 1323, causing the asparagine (N) at amino acid position 441 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.0075
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Benign	0.11
Sift	Benign	0.083	T;D;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.23
MutPred		0.65		Gain of methylation at N441 (P = 0.0061);.;.;
MVP		0.28
MPC		0.10
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.45
gMVP		0.64
Mutation Taster		=39/61	disease causing

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: rs1363033403; hg19: chr1-151337115; COSMIC: COSV106108997; COSMIC: COSV106108997;