15-48992287-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000559471.6(SECISBP2L):ā€‹c.3263A>Gā€‹(p.Asn1088Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,612,600 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000082 ( 1 hom. )

Consequence

SECISBP2L
ENST00000559471.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.454
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016802818).
BP6
Variant 15-48992287-T-C is Benign according to our data. Variant chr15-48992287-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2358706.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SECISBP2LNM_001193489.2 linkuse as main transcriptc.3263A>G p.Asn1088Ser missense_variant 18/18 ENST00000559471.6 NP_001180418.1
SECISBP2LNM_014701.4 linkuse as main transcriptc.3128A>G p.Asn1043Ser missense_variant 17/17 NP_055516.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SECISBP2LENST00000559471.6 linkuse as main transcriptc.3263A>G p.Asn1088Ser missense_variant 18/181 NM_001193489.2 ENSP00000453854 P4Q93073-1
SECISBP2LENST00000261847.7 linkuse as main transcriptc.3128A>G p.Asn1043Ser missense_variant 17/171 ENSP00000261847 A1Q93073-2
SECISBP2LENST00000561428.1 linkuse as main transcriptc.252+511A>G intron_variant 3 ENSP00000454144

Frequencies

GnomAD3 genomes
AF:
0.000335
AC:
51
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000892
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000963
AC:
24
AN:
249272
Hom.:
0
AF XY:
0.0000964
AC XY:
13
AN XY:
134850
show subpopulations
Gnomad AFR exome
AF:
0.000740
Gnomad AMR exome
AF:
0.0000591
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000822
AC:
120
AN:
1460266
Hom.:
1
Cov.:
30
AF XY:
0.0000867
AC XY:
63
AN XY:
726490
show subpopulations
Gnomad4 AFR exome
AF:
0.00123
Gnomad4 AMR exome
AF:
0.0000453
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000328
AC:
50
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000914
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000107
Hom.:
0
Bravo
AF:
0.000325
ESP6500AA
AF:
0.000910
AC:
4
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000123
AC:
15
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.033
DANN
Benign
0.38
DEOGEN2
Benign
0.0076
T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.26
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.37
N;N
REVEL
Benign
0.079
Sift
Benign
0.34
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.0
B;B
Vest4
0.057
MVP
0.21
MPC
0.17
ClinPred
0.011
T
GERP RS
-8.4
Varity_R
0.013
gMVP
0.19

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.

Other links and lift over

dbSNP: rs145854377; hg19: chr15-49284484; API