chr1-151365673-C-A

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003944.4(SELENBP1):​c.934G>T​(p.Asp312Tyr) 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. 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. D312N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Not reported in ClinVar
• 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

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, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENBP1	NM_003944.4	c.934G>T	p.Asp312Tyr	missense_variant	Exon 9 of 12	ENST00000368868.10	NP_003935.2
SELENBP1	NM_001258289.2	c.1060G>T	p.Asp354Tyr	missense_variant	Exon 9 of 12		NP_001245218.1
SELENBP1	NM_001258288.2	c.748G>T	p.Asp250Tyr	missense_variant	Exon 8 of 11		NP_001245217.1
SELENBP1	XM_047433576.1	c.881G>T	p.Arg294Leu	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>T	p.Asp312Tyr	missense_variant	Exon 9 of 12	1	NM_003944.4	ENSP00000357861.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.7	D;D;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.029	D;D;.
Sift4G	Uncertain	0.035	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.97
MutPred		0.92		Gain of helix (P = 0.0854);.;.;
MVP		0.62
MPC		0.49
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.80
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;