15-48992333-G-C

Position:

• chr15-48992333-G-C

Variant summary

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

The ENST00000559471.6(SECISBP2L):​c.3217C>G​(p.Gln1073Glu) variant causes a missense change. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SECISBP2L ENST00000559471.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

Genes affected

SECISBP2L (HGNC:28997): (SECIS binding protein 2 like) Enables RNA binding activity. Predicted to be involved in selenocysteine incorporation. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11832693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECISBP2L	NM_001193489.2	c.3217C>G	p.Gln1073Glu	missense_variant	18/18	ENST00000559471.6	NP_001180418.1
SECISBP2L	NM_014701.4	c.3082C>G	p.Gln1028Glu	missense_variant	17/17		NP_055516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SECISBP2L	ENST00000559471.6	c.3217C>G	p.Gln1073Glu	missense_variant	18/18	1	NM_001193489.2	ENSP00000453854	P4
SECISBP2L	ENST00000261847.7	c.3082C>G	p.Gln1028Glu	missense_variant	17/17	1		ENSP00000261847	A1
SECISBP2L	ENST00000561428.1	c.252+465C>G		intron_variant		3		ENSP00000454144

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.3217C>G (p.Q1073E) alteration is located in exon 18 (coding exon 18) of the SECISBP2L gene. This alteration results from a C to G substitution at nucleotide position 3217, causing the glutamine (Q) at amino acid position 1073 to be replaced by a glutamic acid (E). 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	0.064
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.11
Sift	Benign	0.054	T;T
Sift4G	Benign	0.80	T;T
Polyphen		0.0010	B;B
Vest4		0.20
MutPred		0.075		Loss of glycosylation at P1076 (P = 0.1329);.;
MVP		0.53
MPC		0.23
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.068
gMVP		0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1901996426; hg19: chr15-49284530;