rs5937843

chrX-74529484-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006517.5(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 NM_006517.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0840

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]

ACMG classification

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	UniProt
SLC16A2	NM_006517.5	c.1399+43T>G		intron_variant		ENST00000587091.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A2	ENST00000587091.6	c.1399+43T>G		intron_variant		1	NM_006517.5	P1
SLC16A2	ENST00000590447.1	c.611-1849T>G		intron_variant		5
SLC16A2	ENST00000636771.1	c.*1100+43T>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.576 AC: 63643 AN: 110491 Hom.: 16133 Cov.: 22 AF XY: 0.566 AC XY: 18520 AN XY: 32747

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

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.: 16 AF XY: 0.760 AC XY: 204718 AN XY: 269428

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.: 22 AF XY: 0.565 AC XY: 18552 AN XY: 32807

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

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

Other links and lift over

dbSNP: rs5937843; hg19: chrX-73749319; COSMIC: COSV52084469;