rs1060504685

Variant names:

• chrX-135998934-A-C
• rs1060504685
• NM_001379110.1:c.603A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-135998934-A-C
• chrX-135998934-A-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001379110.1(SLC9A6):​c.603A>C​(p.Leu201Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,089,954 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L201L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: SLC9A6 NM_001379110.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.603A>C	p.Leu201Leu	synonymous_variant	Exon 6 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.603A>C	p.Leu201Leu	synonymous_variant	Exon 6 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.759A>C	p.Leu253Leu	synonymous_variant	Exon 5 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.663A>C	p.Leu221Leu	synonymous_variant	Exon 5 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.603A>C	p.Leu201Leu	synonymous_variant	Exon 6 of 17	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1089954 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 355642

African (AFR) AF: 0.00 AC: 0 AN: 26243

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19319

East Asian (EAS) AF: 0.00 AC: 0 AN: 30147

South Asian (SAS) AF: 0.00 AC: 0 AN: 53943

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40479

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 834681

Other (OTH) AF: 0.00 AC: 0 AN: 45821

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.8
DANN	Benign	0.63
PhyloP100		-0.0050

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1060504685; hg19: chrX-135081093;