chrX-74421660-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006517.5(SLC16A2):c.23G>A(p.Ser8Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 1,202,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000097 ( 0 hom. 39 hem. )

Consequence

SLC16A2
NM_006517.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.657

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00589785).

BP6

Variant X-74421660-G-A is Benign according to our data. Variant chrX-74421660-G-A is described in ClinVar as Benign. ClinVar VariationId is 1575047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000887 (10/112769) while in subpopulation AMR AF = 0.000925 (10/10813). AF 95% confidence interval is 0.000501. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAdExome4 at 39 XL gene

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.23G>A	p.Ser8Asn	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.23G>A	p.Ser8Asn	missense	Exon 1 of 6	ENSP00000465734.1	P36021
SLC16A2	ENST00000878592.1		c.23G>A	p.Ser8Asn	missense	Exon 1 of 7	ENSP00000548651.1
SLC16A2	ENST00000922847.1		c.23G>A	p.Ser8Asn	missense	Exon 1 of 7	ENSP00000592906.1

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112769

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000552

AC:

AN:

161237

AF XY:

0.000506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00336

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:

0.000242

GnomAD4 exome

AF:

0.0000973

AC:

106

AN:

1089706

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

357872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26352

American (AMR)

AF:

0.00306

AC:

106

AN:

34651

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19258

East Asian (EAS)

AF:

0.00

AC:

AN:

30037

South Asian (SAS)

AF:

0.00

AC:

AN:

53229

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3774

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839937

Other (OTH)

AF:

0.00

AC:

AN:

45838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000887

AC:

AN:

112769

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34919

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31080

American (AMR)

AF:

0.000925

AC:

AN:

10813

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3565

South Asian (SAS)

AF:

0.00

AC:

AN:

2718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6259

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53248

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.000323

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

PhyloP100

0.66

PrimateAI

Uncertain

0.55

Sift4G

Benign

0.40

Polyphen

0.079

Vest4

0.15

MutPred

0.095

Loss of phosphorylation at S8 (P = 0.0108)

MVP

0.31

MPC

1.0

ClinPred

0.043

GERP RS

3.0

PromoterAI

0.11

Neutral

(source)

Varity_R

0.15

gMVP

0.21

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over