Variant rs5937843 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000587091.6(SLC16A2):c.1399+43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 110,541 control chromosomes in the GnomAD database, including 16,119 homozygotes. There are 18,552 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 16119 hom., 18552 hem., cov: 22)

Exomes 𝑓: 0.75 ( 199128 hom. 204718 hem. )

Failed GnomAD Quality Control

Consequence

SLC16A2
ENST00000587091.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0840

Variant links:

Genes affected

SLC16A2 (HGNC:10923): (solute carrier family 16 member 2) This gene encodes an integral membrane protein that functions as a transporter of thyroid hormone. The encoded protein facilitates the cellular importation of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). This gene is expressed in many tissues and likely plays an important role in the development of the central nervous system. Loss of function mutations in this gene are associated with psychomotor retardation in males while females exhibit no neurological defects and more moderate thyroid-deficient phenotypes. This gene is subject to X-chromosome inactivation. Mutations in this gene are the cause of Allan-Herndon-Dudley syndrome. [provided by RefSeq, Mar 2012]

SLC16A2 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 (BayesDel_noAF=-0.91).

BP6

Variant X-74529484-T-G is Benign according to our data. Variant chrX-74529484-T-G is described in ClinVar as [Benign]. Clinvar id is 159903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A2	NM_006517.5 linkuse as main transcript	c.1399+43T>G		intron_variant		ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
SLC16A2	ENST00000587091.6 linkuse as main transcript	c.1399+43T>G	intron_variant	1	NM_006517.5	ENSP00000465734	P1
SLC16A2	ENST00000590447.1 linkuse as main transcript	c.611-1849T>G	intron_variant	5		ENSP00000466213
SLC16A2	ENST00000636771.1 linkuse as main transcript	c.*1100+43T>G	intron_variant, NMD_transcript_variant	5		ENSP00000490445

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

63643

AN:

110491

Hom.:

16133

Cov.:

AF XY:

0.566

AC XY:

18520

AN XY:

32747

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.0334

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.720

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.606

AC:

63477

AN:

104815

Hom.:

15361

AF XY:

0.616

AC XY:

20079

AN XY:

32609

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.783

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.777

Gnomad NFE exome

AF:

0.810

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.754

AC:

705707

AN:

935708

Hom.:

199128

Cov.:

AF XY:

0.760

AC XY:

204718

AN XY:

269428

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.781

Gnomad4 EAS exome

AF:

0.0208

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.775

Gnomad4 NFE exome

AF:

0.826

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.576

AC:

63643

AN:

110541

Hom.:

16119

Cov.:

AF XY:

0.565

AC XY:

18552

AN XY:

32807

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.779

Gnomad4 EAS

AF:

0.0332

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.776

Gnomad4 NFE

AF:

0.804

Gnomad4 OTH

AF:

0.601

Alfa

AF:

0.741

Hom.:

69665

Bravo

AF:

0.541

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

Allan-Herndon-Dudley syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.58

DANN

Benign

0.55

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