rs780086745

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM5BP4_StrongBP6BS1BS2

The NM_006517.5(SLC16A2):c.890G>A(p.Arg297His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,209,908 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R297L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000014 ( 0 hom. 9 hem. )

Consequence

SLC16A2
NM_006517.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.0620

Publications

0 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: Orphanet, G2P, ClinGen, 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 -11 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chrX-74524672-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 449964.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.041076183).

BP6

Variant X-74524673-G-A is Benign according to our data. Variant chrX-74524673-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 436738.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000137 (15/1098080) while in subpopulation SAS AF = 0.000222 (12/54148). AF 95% confidence interval is 0.000128. There are 0 homozygotes in GnomAdExome4. There are 9 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A2	NM_006517.5 link	c.890G>A	p.Arg297His	missense_variant	Exon 3 of 6	ENST00000587091.6	NP_006508.2	P36021

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A2	ENST00000587091.6 link	c.890G>A	p.Arg297His	missense_variant	Exon 3 of 6	1	NM_006517.5	ENSP00000465734.1	P36021
SLC16A2	ENST00000590447.1 link	c.329G>A	p.Arg110His	missense_variant	Exon 2 of 4	5		ENSP00000466213.1	K7ELT4
SLC16A2	ENST00000636771.1 link	n.*591G>A		non_coding_transcript_exon_variant	Exon 4 of 7	5		ENSP00000490445.1	A0A1B0GVB4
SLC16A2	ENST00000636771.1 link	n.*591G>A		3_prime_UTR_variant	Exon 4 of 7	5		ENSP00000490445.1	A0A1B0GVB4

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111775

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183261

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1098080

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000222

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40469

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

842035

Other (OTH)

AF:

0.00

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.0000179

AC:

AN:

111828

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

34020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30761

American (AMR)

AF:

0.00

AC:

AN:

10596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3547

South Asian (SAS)

AF:

0.000380

AC:

AN:

2630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53158

Other (OTH)

AF:

0.00

AC:

AN:

1530

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic paraplegia

Benign:1

Nov 09, 2022

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

0.072

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.40

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.69

M_CAP

Benign

0.027

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-0.062

PrimateAI

Benign

0.26

Sift4G

Benign

0.27

Polyphen

0.0020

Vest4

0.014

MutPred

0.51

Loss of MoRF binding (P = 0.0165);

MVP

0.33

MPC

1.1

ClinPred

0.026

GERP RS

-7.7

Varity_R

0.054

gMVP

0.35

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over