1-151365673-C-T

Variant names:

• chr1-151365673-C-T
• rs181909137
• NM_003944.4:c.934G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003944.4(SELENBP1):​c.934G>A​(p.Asp312Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

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.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENBP1	NM_003944.4	c.934G>A	p.Asp312Asn	missense_variant	Exon 9 of 12	ENST00000368868.10	NP_003935.2
SELENBP1	NM_001258289.2	c.1060G>A	p.Asp354Asn	missense_variant	Exon 9 of 12		NP_001245218.1
SELENBP1	NM_001258288.2	c.748G>A	p.Asp250Asn	missense_variant	Exon 8 of 11		NP_001245217.1
SELENBP1	XM_047433576.1	c.881G>A	p.Arg294Gln	missense_variant	Exon 8 of 9		XP_047289532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENBP1	ENST00000368868.10	c.934G>A	p.Asp312Asn	missense_variant	Exon 9 of 12	1	NM_003944.4	ENSP00000357861.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152154 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: 0.000386

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

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251464 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33480

Gnomad4 AMR exome AF: 0.0000447 AC: 2 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.000252 AC: 10 AN: 39700

Gnomad4 SAS exome AF: 0.0000812 AC: 7 AN: 86250

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53420

Gnomad4 NFE exome AF: 0.00000629 AC: 7 AN: 1112010

Gnomad4 Remaining exome AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74458

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: 0.000387 AC: 0.000386548 AN: 0.000386548

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000147037 AN: 0.0000147037

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000819 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.934G>A (p.D312N) alteration is located in exon 9 (coding exon 9) of the SELENBP1 gene. This alteration results from a G to A substitution at nucleotide position 934, causing the aspartic acid (D) at amino acid position 312 to be replaced by an asparagine (N). 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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D;.;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.3	M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.8	D;D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.020	D;D;.
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.93
MVP		0.53
MPC		0.40
ClinPred		0.89	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.85
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs181909137; hg19: chr1-151338149;