rs146263125

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001379110.1(SLC9A6):c.1637G>A(p.Arg546Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,172,230 control chromosomes in the GnomAD database, including 2 homozygotes. There are 751 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R546W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., 45 hem., cov: 22)

Exomes 𝑓: 0.0022 ( 1 hom. 706 hem. )

Consequence

SLC9A6
NM_001379110.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 9.60

Publications

10 publications found

Variant links:

Genes affected

SLC9A6 (HGNC:11079): (solute carrier family 9 member A6) This gene encodes a sodium-hydrogen exchanger that is amember of the solute carrier family 9. The encoded protein localizes to early and recycling endosomes and may be involved in regulating endosomal pH and volume. Defects in this gene are associated with X-linked syndromic cognitive disability, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

SLC9A6 Gene-Disease associations (from GenCC):

Christianson syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

SLC9A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-136033469-G-A is Benign according to our data. Variant chrX-136033469-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00156 (172/110571) while in subpopulation NFE AF = 0.00255 (135/52858). AF 95% confidence interval is 0.0022. There are 1 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 45 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A6	NM_001379110.1	MANE Select	c.1637G>A	p.Arg546Gln	missense	Exon 16 of 18	NP_001366039.1	A0A0D9SGH0
SLC9A6	NM_001438742.1		c.1793G>A	p.Arg598Gln	missense	Exon 15 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.1703G>A	p.Arg568Gln	missense	Exon 14 of 16	NP_001036002.1	Q92581-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1637G>A	p.Arg546Gln	missense	Exon 16 of 18	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8	TSL:1	c.1703G>A	p.Arg568Gln	missense	Exon 14 of 16	ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7	TSL:1	c.1607G>A	p.Arg536Gln	missense	Exon 14 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

172

AN:

110521

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00192

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:

0.00255

Gnomad OTH

AF:

0.00134

GnomAD2 exomes

AF:

0.00166

AC:

304

AN:

182996

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00221

AC:

2349

AN:

1061659

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

706

AN XY:

332559

show subpopulations

African (AFR)

AF:

0.000429

AC:

AN:

25629

American (AMR)

AF:

0.000894

AC:

AN:

34659

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18593

East Asian (EAS)

AF:

0.00

AC:

AN:

28926

South Asian (SAS)

AF:

0.0000751

AC:

AN:

53280

European-Finnish (FIN)

AF:

0.000335

AC:

AN:

38813

Middle Eastern (MID)

AF:

0.000261

AC:

AN:

3834

European-Non Finnish (NFE)

AF:

0.00272

AC:

2217

AN:

813616

Other (OTH)

AF:

0.00162

AC:

AN:

44309

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00156

AC:

172

AN:

110571

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

32859

show subpopulations

African (AFR)

AF:

0.000493

AC:

AN:

30406

American (AMR)

AF:

0.00192

AC:

AN:

10414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5743

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00255

AC:

135

AN:

52858

Other (OTH)

AF:

0.00133

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00215

Hom.:

107

Bravo

AF:

0.00133

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00312

AC:

ExAC

AF:

0.00158

AC:

192

EpiCase

AF:

0.00191

EpiControl

AF:

0.00202

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (4)

Christianson syndrome (1)

Inborn genetic diseases (1)

Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.6

PhyloP100

9.6

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.43

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.92

Vest4

0.42

MVP

0.74

MPC

2.3

ClinPred

0.044

GERP RS

5.2

Varity_R

0.84

gMVP

0.94

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: 24

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