Variant 15-48992644-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001193489.2(SECISBP2L):c.2906G>A(p.Arg969Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SECISBP2L
NM_001193489.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Variant links:

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]

SECISBP2L links:

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ACMG classification

Classification made for transcript

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=0.3192764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECISBP2L	NM_001193489.2 linkuse as main transcript	c.2906G>A	p.Arg969Gln	missense_variant	18/18	ENST00000559471.6	NP_001180418.1	Q93073-1A0A024R5R0
SECISBP2L	NM_014701.4 linkuse as main transcript	c.2771G>A	p.Arg924Gln	missense_variant	17/17		NP_055516.2	Q93073-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SECISBP2L	ENST00000559471.6 linkuse as main transcript	c.2906G>A	p.Arg969Gln	missense_variant	18/18	1	NM_001193489.2	ENSP00000453854.1	Q93073-1
SECISBP2L	ENST00000261847.7 linkuse as main transcript	c.2771G>A	p.Arg924Gln	missense_variant	17/17	1		ENSP00000261847.3	Q93073-2
SECISBP2L	ENST00000561428.1 linkuse as main transcript	c.250+154G>A		intron_variant		3		ENSP00000454144.1	H0YNT4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251304

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.2906G>A (p.R969Q) alteration is located in exon 18 (coding exon 18) of the SECISBP2L gene. This alteration results from a G to A substitution at nucleotide position 2906, causing the arginine (R) at amino acid position 969 to be replaced by a glutamine (Q). 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

0.22

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.032

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.32

T;T

MetaSVM

Uncertain

-0.046

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.65

N;N

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.045

D;D

Polyphen

1.0

D;D

Vest4

0.38

MutPred

0.23

Loss of phosphorylation at S967 (P = 0.1438);.;

MVP

0.75

MPC

0.30

ClinPred

0.29

GERP RS

5.2

Varity_R

0.49

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over