9-89325597-G-A

Position:

• chr9-89325597-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024077.5(SECISBP2):​c.353G>A​(p.Cys118Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SECISBP2 NM_024077.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.491

Genes affected

SECISBP2 (HGNC:30972): (SECIS binding protein 2) The protein encoded by this gene is one of the essential components of the machinery involved in co-translational insertion of selenocysteine (Sec) into selenoproteins. Sec is encoded by the UGA codon, which normally signals translation termination. The recoding of UGA as Sec codon requires a Sec insertion sequence (SECIS) element; present in the 3' untranslated regions of eukaryotic selenoprotein mRNAs. This protein specifically binds to the SECIS element, which is stimulated by a Sec-specific translation elongation factor. Mutations in this gene have been associated with reduction in enzymatic activity of type II iodothyronine deiodinase (a selenoprotein) and abnormal thyroid hormone metabolism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]

SECISBP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22138879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECISBP2	NM_024077.5	c.353G>A	p.Cys118Tyr	missense_variant	3/17	ENST00000375807.8	NP_076982.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SECISBP2	ENST00000375807.8	c.353G>A	p.Cys118Tyr	missense_variant	3/17	1	NM_024077.5	ENSP00000364965.3
SECISBP2	ENST00000339901.8	c.134G>A	p.Cys45Tyr	missense_variant	3/17	1		ENSP00000364959.3
SECISBP2	ENST00000470305.1	n.3398G>A		non_coding_transcript_exon_variant	1/3	1
SECISBP2	ENST00000534113.6	c.149G>A	p.Cys50Tyr	missense_variant	3/17	2		ENSP00000436650.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.353G>A (p.C118Y) alteration is located in exon 3 (coding exon 3) of the SECISBP2 gene. This alteration results from a G to A substitution at nucleotide position 353, causing the cysteine (C) at amino acid position 118 to be replaced by a tyrosine (Y). 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	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.3
DANN	Benign	0.25
DEOGEN2	Benign	0.0070	T;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.26	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.26
MutPred		0.69		Gain of phosphorylation at C118 (P = 0.0879);.;.;
MVP		0.64
MPC		0.097
ClinPred		0.12	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-91940512;