dbSNP rs1556614706: SLC9A6:p.Arg3Arg (chrX-135985511-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001438742.1(SLC9A6):c.9G>C(p.Arg3Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 993,662 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 21)

Exomes 𝑓: 0.0000010 ( 0 hom. 0 hem. )

Consequence

SLC9A6
NM_001438742.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0820

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, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

SLC9A6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-135985511-G-C is Benign according to our data. Variant chrX-135985511-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1156645.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438742.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A6	NM_001379110.1	MANE Select	c.-57+34G>C		intron	N/A	NP_001366039.1	A0A0D9SGH0
SLC9A6	NM_001438742.1		c.9G>C	p.Arg3Arg	synonymous	Exon 1 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.9G>C	p.Arg3Arg	synonymous	Exon 1 of 16	NP_001036002.1	Q92581-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A6	ENST00000370695.8	TSL:1	c.9G>C	p.Arg3Arg	synonymous	Exon 1 of 16	ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7	TSL:1	c.9G>C	p.Arg3Arg	synonymous	Exon 1 of 16	ENSP00000359732.3	Q92581-1
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.-57+34G>C		intron	N/A	ENSP00000487486.2	A0A0D9SGH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000101

AC:

AN:

993662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

311742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22710

American (AMR)

AF:

0.00

AC:

AN:

21200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15001

East Asian (EAS)

AF:

0.00

AC:

AN:

26051

South Asian (SAS)

AF:

0.00

AC:

AN:

42334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2772

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

795695

Other (OTH)

AF:

0.0000238

AC:

AN:

42019

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Christianson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.082

PromoterAI

0.057

Neutral

(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

Computational scores

Splicing

Publications

Other links and lift over