dbSNP rs1556619315: SLC9A6:p.Val388Val (chrX-136016728-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1

The NM_001379110.1(SLC9A6):c.1164C>T(p.Val388Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,050,982 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000038 ( 0 hom. 1 hem. )

Consequence

SLC9A6
NM_001379110.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.09

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant X-136016728-C-T is Benign according to our data. Variant chrX-136016728-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 469633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000381 (4/1050982) while in subpopulation AMR AF = 0.000115 (4/34663). AF 95% confidence interval is 0.0000389. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 24. This position passed quality control check.

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.1164C>T	p.Val388Val	synonymous	Exon 11 of 18	NP_001366039.1
SLC9A6	NM_001438742.1		c.1320C>T	p.Val440Val	synonymous	Exon 10 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.1320C>T	p.Val440Val	synonymous	Exon 10 of 16	NP_001036002.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.1164C>T	p.Val388Val	synonymous	Exon 11 of 18	ENSP00000487486.2
SLC9A6	ENST00000370695.8	TSL:1	c.1320C>T	p.Val440Val	synonymous	Exon 10 of 16	ENSP00000359729.4
SLC9A6	ENST00000370698.7	TSL:1	c.1224C>T	p.Val408Val	synonymous	Exon 10 of 16	ENSP00000359732.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000381

AC:

AN:

1050982

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

322294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25513

American (AMR)

AF:

0.000115

AC:

AN:

34663

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19007

East Asian (EAS)

AF:

0.00

AC:

AN:

30013

South Asian (SAS)

AF:

0.00

AC:

AN:

52125

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40501

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3996

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

800593

Other (OTH)

AF:

0.00

AC:

AN:

44571

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC9A6: BP4

Christianson syndrome

Benign:1

Jul 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

6.4

(source)

DANN

Benign

0.78

PhyloP100

3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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