rs797045973

chrX-135985823-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001379110.1(SLC9A6):c.165T>G(p.Ile55Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I55V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLC9A6 NM_001379110.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.161

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A6	NM_001379110.1	c.165T>G	p.Ile55Met	missense_variant	2/18	ENST00000630721.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A6	ENST00000630721.3	c.165T>G	p.Ile55Met	missense_variant	2/18	4	NM_001379110.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 19, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Pathogenic	27
Dann	Uncertain	0.98
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
Polyphen		0.84, 0.74	.;.;.;.;.;.;P;P;.;.
Vest4		0.42, 0.43, 0.42
MutPred		0.65		.;.;.;.;.;.;Loss of catalytic residue at I107 (P = 0.0018);Loss of catalytic residue at I107 (P = 0.0018);.;.;
MVP		0.20
MPC		1.3
ClinPred		0.73	D
GERP RS		1.9
Varity_R		0.36
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.70		Position offset: -1
DS_DL_spliceai		0.29		Position offset: 4

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

Publications

LitVar

Other links and lift over

dbSNP: rs797045973; hg19: chrX-135067982;