15-48996520-C-T

Position:

• chr15-48996520-C-T

Variant summary

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

The ENST00000559471.6(SECISBP2L):​c.2470G>A​(p.Ala824Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SECISBP2L ENST00000559471.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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=0.25646138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECISBP2L	NM_001193489.2	c.2470G>A	p.Ala824Thr	missense_variant	17/18	ENST00000559471.6	NP_001180418.1
SECISBP2L	NM_014701.4	c.2335G>A	p.Ala779Thr	missense_variant	16/17		NP_055516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SECISBP2L	ENST00000559471.6	c.2470G>A	p.Ala824Thr	missense_variant	17/18	1	NM_001193489.2	ENSP00000453854	P4
SECISBP2L	ENST00000261847.7	c.2335G>A	p.Ala779Thr	missense_variant	16/17	1		ENSP00000261847	A1
SECISBP2L	ENST00000380927.6	c.1756G>A	p.Ala586Thr	missense_variant	17/17	1		ENSP00000370314
SECISBP2L	ENST00000561428.1			upstream_gene_variant		3		ENSP00000454144

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.2470G>A (p.A824T) alteration is located in exon 17 (coding exon 17) of the SECISBP2L gene. This alteration results from a G to A substitution at nucleotide position 2470, causing the alanine (A) at amino acid position 824 to be replaced by a threonine (T). 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	0.084
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.084	T;T;T
Sift4G	Benign	0.84	T;T;.
Polyphen		0.67	P;P;.
Vest4		0.19
MutPred		0.24		Gain of glycosylation at A824 (P = 0.024);.;.;
MVP		0.74
MPC		0.21
ClinPred		0.49	T
GERP RS		4.9
Varity_R		0.065
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-49288717;