rs1556619324

Variant names:

• chrX-136016754-C-A
• rs1556619324
• NM_001379110.1:c.1190C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001379110.1(SLC9A6):​c.1190C>A​(p.Ala397Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC9A6 NM_001379110.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.1190C>A	p.Ala397Glu	missense_variant	Exon 11 of 18	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000630721.3	c.1190C>A	p.Ala397Glu	missense_variant	Exon 11 of 18	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370695.8	c.1346C>A	p.Ala449Glu	missense_variant	Exon 10 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.1250C>A	p.Ala417Glu	missense_variant	Exon 10 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000370701.6	c.1190C>A	p.Ala397Glu	missense_variant	Exon 11 of 17	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 919678 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 249822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amblyopia;C0004106:Astigmatism;C0020490:Hypermetropia;C0020517:Allergy;C0023520:Leukodystrophy;C0036572:Seizure;C0038379:Strabismus;C0240379:Open mouth;C0349588:Short stature;C0454644:Delayed speech and language development;C1854301:Motor delay;C4021217:EEG with generalized slow activity;C4551563:Microcephaly Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;.;.;.;.;.;.;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;.;D;.;.;D;D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	.;.;.;.;.;.;.;M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.4	.;.;.;.;.;D;D;D;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	.;.;.;.;.;D;D;D;.
Sift4G	Uncertain	0.0030	.;.;.;.;.;D;D;D;.
Polyphen		1.0	.;.;.;.;.;.;D;D;.
Vest4		0.84, 0.83, 0.85
MutPred		0.77		.;.;.;.;.;.;.;Loss of glycosylation at T412 (P = 0.2445);.;
MVP		0.76
MPC		2.4
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.99
gMVP		1.0

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

LitVar

Other links and lift over

dbSNP: rs1556619324; hg19: chrX-135098913;