rs377126261

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001379110.1(SLC9A6):c.338A>G(p.Asn113Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000711 in 1,196,337 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000066 ( 0 hom. 25 hem. )

Consequence

SLC9A6
NM_001379110.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Publications

0 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, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen

SLC9A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22252855).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000116 (13/112460) while in subpopulation NFE AF = 0.000187 (10/53355). AF 95% confidence interval is 0.000101. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.338A>G	p.Asn113Ser	missense_variant	Exon 3 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC9A6	ENST00000630721.3 link	c.338A>G	p.Asn113Ser	missense_variant	Exon 3 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8 link	c.494A>G	p.Asn165Ser	missense_variant	Exon 2 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370701.6 link	c.338A>G	p.Asn113Ser	missense_variant	Exon 3 of 17	1		ENSP00000359735.1
SLC9A6	ENST00000370698.7 link	c.429+65A>G		intron_variant	Intron 2 of 15	1		ENSP00000359732.3

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000187

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000601

AC:

AN:

182977

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000613

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1083877

Hom.:

Cov.:

AF XY:

0.0000714

AC XY:

AN XY:

350059

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26159

American (AMR)

AF:

0.000114

AC:

AN:

35174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19292

East Asian (EAS)

AF:

0.00

AC:

AN:

30132

South Asian (SAS)

AF:

0.0000372

AC:

AN:

53766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4055

European-Non Finnish (NFE)

AF:

0.0000784

AC:

AN:

829209

Other (OTH)

AF:

0.0000219

AC:

AN:

45577

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000116

AC:

AN:

112460

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34612

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

30941

American (AMR)

AF:

0.00

AC:

AN:

10550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3619

South Asian (SAS)

AF:

0.00

AC:

AN:

2755

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6153

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000187

AC:

AN:

53355

Other (OTH)

AF:

0.00

AC:

AN:

1513

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:

0.000108

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 04, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

.;.;.;.;.;.;T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

.;.;.;.;D;D;D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

7.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.3

.;.;.;.;N;N;.;.

REVEL

Benign

0.089

Sift

Benign

0.52

.;.;.;.;T;T;.;.

Sift4G

Benign

0.61

.;.;.;.;T;T;T;.

Polyphen

0.022

.;.;.;.;.;B;.;.

Vest4

0.24, 0.24

MVP

0.31

MPC

0.96

ClinPred

0.49

GERP RS

5.1

gMVP

0.59

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over