1-151364974-G-C

Variant names:

• chr1-151364974-G-C
• NM_003944.4:c.1208C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003944.4(SELENBP1):​c.1208C>G​(p.Thr403Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,632 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. T403M) has been classified as Benign.

• 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: 6.25

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENBP1	NM_003944.4	c.1208C>G	p.Thr403Arg	missense_variant	Exon 11 of 12	ENST00000368868.10	NP_003935.2
SELENBP1	NM_001258289.2	c.1334C>G	p.Thr445Arg	missense_variant	Exon 11 of 12		NP_001245218.1
SELENBP1	NM_001258288.2	c.1022C>G	p.Thr341Arg	missense_variant	Exon 10 of 11		NP_001245217.1
SELENBP1	XM_047433576.1	c.*345C>G		downstream_gene_variant			XP_047289532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENBP1	ENST00000368868.10	c.1208C>G	p.Thr403Arg	missense_variant	Exon 11 of 12	1	NM_003944.4	ENSP00000357861.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461632 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.94	P;.;.
Vest4		0.84
MutPred		0.75		Gain of MoRF binding (P = 0.018);.;.;
MVP		0.41
MPC		0.49
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.61
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr1-151337450;