1-151365626-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_003944.4(SELENBP1):​c.981G>C​(p.Trp327Cys) variant causes a missense 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SELENBP1
NM_003944.4 missense

Scores

12
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENBP1NM_003944.4 linkuse as main transcriptc.981G>C p.Trp327Cys missense_variant 9/12 ENST00000368868.10
SELENBP1NM_001258289.2 linkuse as main transcriptc.1107G>C p.Trp369Cys missense_variant 9/12
SELENBP1NM_001258288.2 linkuse as main transcriptc.795G>C p.Trp265Cys missense_variant 8/11
SELENBP1XM_047433576.1 linkuse as main transcriptc.928G>C p.Ala310Pro missense_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENBP1ENST00000368868.10 linkuse as main transcriptc.981G>C p.Trp327Cys missense_variant 9/121 NM_003944.4 P1Q13228-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2023The c.981G>C (p.W327C) alteration is located in exon 9 (coding exon 9) of the SELENBP1 gene. This alteration results from a G to C substitution at nucleotide position 981, causing the tryptophan (W) at amino acid position 327 to be replaced by a cysteine (C). 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
0.97
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
D;.;.
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Pathogenic
3.3
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-13
D;D;.
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.97
MutPred
0.94
Gain of catalytic residue at L328 (P = 0.0668);.;.;
MVP
0.39
MPC
0.60
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.91
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151338102; API