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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1 link	c.1164C>T	p.Val388Val	synonymous_variant	Exon 11 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9A6	ENST00000630721.3 link	c.1164C>T	p.Val388Val	synonymous_variant	Exon 11 of 18	4	NM_001379110.1	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8 link	c.1320C>T	p.Val440Val	synonymous_variant	Exon 10 of 16	1		ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7 link	c.1224C>T	p.Val408Val	synonymous_variant	Exon 10 of 16	1		ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000370701.6 link	c.1164C>T	p.Val388Val	synonymous_variant	Exon 11 of 17	1		ENSP00000359735.1	Q92581-3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over