rs6647476

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:13O:1

Conservation

PhyloP100: -0.611

Publications

40 publications found

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 Gene-Disease associations (from GenCC):

Allan-Herndon-Dudley syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

SLC16A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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/Likely_benign. ClinVar VariationId is 21462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A2	NM_006517.5	MANE Select	c.97T>C	p.Ser33Pro	missense	Exon 1 of 6	NP_006508.2	P36021

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A2	ENST00000587091.6	TSL:1 MANE Select	c.97T>C	p.Ser33Pro	missense	Exon 1 of 6	ENSP00000465734.1	P36021
SLC16A2	ENST00000878592.1		c.97T>C	p.Ser33Pro	missense	Exon 1 of 7	ENSP00000548651.1
SLC16A2	ENST00000922847.1		c.97T>C	p.Ser33Pro	missense	Exon 1 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

57031

AN:

109956

Hom.:

11180

Cov.:

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

GnomAD2 exomes

AF:

0.490

AC:

56761

AN:

115862

AF XY:

0.501

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 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

African (AFR)

AF:

0.697

AC:

17751

AN:

25471

American (AMR)

AF:

0.345

AC:

10119

AN:

29364

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

6570

AN:

18715

East Asian (EAS)

AF:

0.971

AC:

27479

AN:

28314

South Asian (SAS)

AF:

0.632

AC:

32061

AN:

50699

European-Finnish (FIN)

AF:

0.531

AC:

16923

AN:

31900

Middle Eastern (MID)

AF:

0.315

AC:

996

AN:

3164

European-Non Finnish (NFE)

AF:

0.413

AC:

339305

AN:

820808

Other (OTH)

AF:

0.466

AC:

20765

AN:

44553

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10483

20966

31450

41933

52416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11754

23508

35262

47016

58770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.690

AC:

20854

AN:

30244

American (AMR)

AF:

0.419

AC:

4426

AN:

10561

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

932

AN:

2609

East Asian (EAS)

AF:

0.959

AC:

3289

AN:

3431

South Asian (SAS)

AF:

0.647

AC:

1663

AN:

2570

European-Finnish (FIN)

AF:

0.545

AC:

3176

AN:

5826

Middle Eastern (MID)

AF:

0.335

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.416

AC:

21807

AN:

52394

Other (OTH)

AF:

0.448

AC:

674

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

934

1868

2801

3735

4669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (2)

Allan-Herndon-Dudley syndrome (2)

Hereditary spastic paraplegia (1)

Inborn genetic diseases (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.5

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-1.6

PhyloP100

-0.61

PrimateAI

Uncertain

0.51

Sift4G

Benign

1.0

Polyphen

0.90

Vest4

0.035

MPC

1.1

ClinPred

0.015

PromoterAI

0.052

Neutral

(source)

Varity_R

0.17

gMVP

0.070

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over