9-89325570-C-G

Variant names:

• chr9-89325570-C-G
• NM_024077.5:c.326C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001354702.2(SECISBP2):​c.-522C>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SECISBP2 NM_001354702.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3448505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECISBP2	NM_024077.5	c.326C>G	p.Ser109Cys	missense_variant	Exon 3 of 17	ENST00000375807.8	NP_076982.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SECISBP2	ENST00000375807.8	c.326C>G	p.Ser109Cys	missense_variant	Exon 3 of 17	1	NM_024077.5	ENSP00000364965.3
SECISBP2	ENST00000339901.8	c.107C>G	p.Ser36Cys	missense_variant	Exon 3 of 17	1		ENSP00000364959.3
SECISBP2	ENST00000470305.1	n.3371C>G		non_coding_transcript_exon_variant	Exon 1 of 3	1
SECISBP2	ENST00000534113.6	c.122C>G	p.Ser41Cys	missense_variant	Exon 3 of 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

May 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.326C>G (p.S109C) alteration is located in exon 3 (coding exon 3) of the SECISBP2 gene. This alteration results from a C to G substitution at nucleotide position 326, causing the serine (S) at amino acid position 109 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	Benign	0.086
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.038	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.44
MutPred		0.33		Gain of sheet (P = 0.039);.;.;
MVP		0.83
MPC		0.35
ClinPred		0.68	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr9-91940485;