9-89325666-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024077.5(SECISBP2):c.422C>T(p.Ala141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,108 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 23 hom. )

Consequence

SECISBP2
NM_024077.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.207

Variant links:

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]

SECISBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021318197).

BP6

Variant 9-89325666-C-T is Benign according to our data. Variant chr9-89325666-C-T is described in ClinVar as [Benign]. Clinvar id is 705949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-89325666-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00837 (1275/152252) while in subpopulation AFR AF= 0.0295 (1227/41546). AF 95% confidence interval is 0.0282. There are 15 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SECISBP2	NM_024077.5 link	c.422C>T	p.Ala141Val	missense_variant	Exon 3 of 17	ENST00000375807.8	NP_076982.3	Q96T21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SECISBP2	ENST00000375807.8 link	c.422C>T	p.Ala141Val	missense_variant	Exon 3 of 17	1	NM_024077.5	ENSP00000364965.3	Q96T21-1
SECISBP2	ENST00000339901.8 link	c.203C>T	p.Ala68Val	missense_variant	Exon 3 of 17	1		ENSP00000364959.3	Q96T21-2
SECISBP2	ENST00000470305.1 link	n.3467C>T		non_coding_transcript_exon_variant	Exon 1 of 3	1
SECISBP2	ENST00000534113.6 link	c.218C>T	p.Ala73Val	missense_variant	Exon 3 of 17	2		ENSP00000436650.2	Q96T21-3

Frequencies

GnomAD3 genomes

AF:

0.00839

AC:

1276

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00234

AC:

588

AN:

251424

Hom.:

AF XY:

0.00155

AC XY:

211

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0337

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000936

AC:

1368

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000788

AC XY:

573

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0354

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00837

AC:

1275

AN:

152252

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.0101

ESP6500AA

AF:

0.0347

AC:

153

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00272

AC:

330

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.068

T;D;T

Polyphen

0.65

P;P;.

Vest4

0.24

MVP

0.70

MPC

0.098

ClinPred

0.017

GERP RS

2.5

Varity_R

0.056

gMVP

0.040

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