rs151178361

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP7BP5_StrongBS1BS2BP4

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Leu381= variant in SLC9A6 (NM_006359.2) is 0.024% in European (Non-Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The silent p.Leu381= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). The p.Leu381= variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2_strong). The p.Leu381= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Leu381= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BS1, BP4, BP7, BS2_strong, BP5_strong). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10524772/MONDO:0010278/033

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00020 ( 0 hom. 56 hem. )

Consequence

SLC9A6
NM_001379110.1 splice_region, synonymous

Scores

2

Clinical Significance

Benign reviewed by expert panel U:1B:6

Conservation

PhyloP100: 2.15

Publications

2 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 -14 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP5

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BS1

For more information check the summary or visit ClinGen Evidence Repository.

BS2

For more information check the summary or visit ClinGen Evidence Repository.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	NM_001379110.1	MANE Select	c.1083G>A	p.Leu361Leu	splice_region synonymous	Exon 11 of 18	NP_001366039.1	A0A0D9SGH0
	SLC9A6	NM_001438742.1		c.1239G>A	p.Leu413Leu	splice_region synonymous	Exon 10 of 17	NP_001425671.1
	SLC9A6	NM_001042537.2		c.1239G>A	p.Leu413Leu	splice_region synonymous	Exon 10 of 16	NP_001036002.1	Q92581-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1083G>A	p.Leu361Leu	splice_region synonymous	Exon 11 of 18	ENSP00000487486.2	A0A0D9SGH0
	SLC9A6	ENST00000370695.8	TSL:1	c.1239G>A	p.Leu413Leu	splice_region synonymous	Exon 10 of 16	ENSP00000359729.4	Q92581-2
	SLC9A6	ENST00000370698.7	TSL:1	c.1143G>A	p.Leu381Leu	splice_region synonymous	Exon 10 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

23

AN:

111993

Hom.:

0

Cov.:

22

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000664

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:

0.000263

Gnomad OTH

AF:

0.000663

GnomAD2 exomes

AF:

0.000148

AC:

27

AN:

182825

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000198

AC:

199

AN:

1004844

Hom.:

0

Cov.:

21

AF XY:

0.000184

AC XY:

56

AN XY:

304198

show subpopulations

African (AFR)

AF:

0.00

AC:

0

AN:

24668

American (AMR)

AF:

0.000143

AC:

5

AN:

35046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

0

AN:

18790

East Asian (EAS)

AF:

0.00

AC:

0

AN:

29772

South Asian (SAS)

AF:

0.00

AC:

0

AN:

52140

European-Finnish (FIN)

AF:

0.00

AC:

0

AN:

40444

Middle Eastern (MID)

AF:

0.00

AC:

0

AN:

3919

European-Non Finnish (NFE)

AF:

0.000246

AC:

186

AN:

757087

Other (OTH)

AF:

0.000186

AC:

8

AN:

42978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0

7

14

22

29

36

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

0

10

20

30

40

50

<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:

0.000205

AC:

23

AN:

111993

Hom.:

0

Cov.:

22

AF XY:

0.000322

AC XY:

11

AN XY:

34163

show subpopulations

African (AFR)

AF:

0.0000324

AC:

1

AN:

30829

American (AMR)

AF:

0.000664

AC:

7

AN:

10538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

0

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

0

AN:

3594

South Asian (SAS)

AF:

0.00

AC:

0

AN:

2693

European-Finnish (FIN)

AF:

0.00

AC:

0

AN:

6053

Middle Eastern (MID)

AF:

0.00

AC:

0

AN:

235

European-Non Finnish (NFE)

AF:

0.000263

AC:

14

AN:

53208

Other (OTH)

AF:

0.000663

AC:

1

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0

2

3

5

6

8

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

0

2

4

6

8

10

<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:

0.000427

Hom.:

2

Bravo

AF:

0.000178

EpiCase

AF:

0.000600

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

-

1

2

not provided (3)

-

-

2

Christianson syndrome (2)

-

-

1

History of neurodevelopmental disorder (1)

-

-

1

SLC9A6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

15

DANN

Benign

0.91

PhyloP100

2.2

Mutation Taster

=93/7

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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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Other links and lift over

dbSNP: rs151178361; hg19: chrX-135098806; API