X-136013427-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001379110.1(SLC9A6):c.1070G>C(p.Arg357Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,063,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

SLC9A6
NM_001379110.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.32

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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
SLC9A6	NM_001379110.1	MANE Select	c.1070G>C	p.Arg357Thr	missense	Exon 10 of 18	NP_001366039.1
SLC9A6	NM_001438742.1		c.1226G>C	p.Arg409Thr	missense	Exon 9 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.1226G>C	p.Arg409Thr	missense	Exon 9 of 16	NP_001036002.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1070G>C	p.Arg357Thr	missense	Exon 10 of 18	ENSP00000487486.2
SLC9A6	ENST00000370695.8	TSL:1	c.1226G>C	p.Arg409Thr	missense	Exon 9 of 16	ENSP00000359729.4
SLC9A6	ENST00000370698.7	TSL:1	c.1130G>C	p.Arg377Thr	missense	Exon 9 of 16	ENSP00000359732.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1063098

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

331228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25781

American (AMR)

AF:

0.00

AC:

AN:

35127

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19127

East Asian (EAS)

AF:

0.00

AC:

AN:

29964

South Asian (SAS)

AF:

0.00

AC:

AN:

53268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40355

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3852

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

810698

Other (OTH)

AF:

0.00

AC:

AN:

44926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Uncertain:1

Sep 10, 2019

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.57

PhyloP100

9.3

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

Sift4G

Benign

0.15

Polyphen

0.18

Vest4

0.83

MutPred

0.54

Gain of ubiquitination at K379 (P = 0.123)

MVP

0.85

MPC

2.6

ClinPred

0.99

GERP RS

5.7

Varity_R

0.94

gMVP

0.89

Mutation Taster

=45/55

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over