X-74421734-T-C

Position:

chrX-74421734-T-C

Variant summary

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

The NM_006517.5(SLC16A2):c.97T>C(p.Ser33Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,052,988 control chromosomes in the GnomAD database, including 74,870 homozygotes. There are 155,511 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 11194 hom., 17145 hem., cov: 23)

Exomes 𝑓: 0.45 ( 74870 hom. 155511 hem. )

Failed GnomAD Quality Control

Consequence

SLC16A2
NM_006517.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -0.611

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 (MetaRNN=1.3504705E-6).

BP6

Variant X-74421734-T-C is Benign according to our data. Variant chrX-74421734-T-C is described in ClinVar as [Benign]. Clinvar id is 21462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-74421734-T-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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.97T>C	p.Ser33Pro	missense_variant	1/6	ENST00000587091.6	NP_006508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A2	ENST00000587091.6 linkuse as main transcript	c.97T>C	p.Ser33Pro	missense_variant	1/6	1	NM_006517.5	ENSP00000465734	P1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

57031

AN:

109956

Hom.:

11180

Cov.:

AF XY:

0.529

AC XY:

17098

AN XY:

32348

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.959

Gnomad SAS

AF:

0.649

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.490

AC:

56761

AN:

115862

Hom.:

10529

AF XY:

0.501

AC XY:

18765

AN XY:

37482

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.959

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.448

AC:

471969

AN:

1052988

Hom.:

74870

Cov.:

AF XY:

0.458

AC XY:

155511

AN XY:

339426

show subpopulations

Gnomad4 AFR exome

AF:

0.697

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.971

Gnomad4 SAS exome

AF:

0.632

Gnomad4 FIN exome

AF:

0.531

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.519

AC:

57093

AN:

110004

Hom.:

11194

Cov.:

AF XY:

0.529

AC XY:

17145

AN XY:

32406

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.959

Gnomad4 SAS

AF:

0.647

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.448

Alfa

AF:

0.445

Hom.:

22231

Bravo

AF:

0.512

TwinsUK

AF:

0.406

AC:

1507

ALSPAC

AF:

0.415

AC:

1199

ESP6500AA

AF:

0.624

AC:

2247

ESP6500EA

AF:

0.370

AC:

2383

ExAC

AF:

0.447

AC:

46125

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 30, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Allan-Herndon-Dudley syndrome

Benign:1Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2015

This alteration is classified as 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. -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.5

DANN

Benign

0.11

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.51

Sift4G

Benign

1.0

Polyphen

0.90

Vest4

0.035

MPC

1.1

ClinPred

0.015

Varity_R

0.17

gMVP

0.070

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