ENST00000370695.8:c.1A>C

Variant names:

• chrX-135985503-A-C
• ENST00000370695.8:c.1A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The ENST00000370695.8(SLC9A6):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,421 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000010 (0 hom. 1 hem.)
• Consequence: SLC9A6 ENST00000370695.8 initiator_codon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

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.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 25 codons. Genomic position: 135985575. Lost 0.035 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A6	NM_001379110.1	c.-57+26A>C		intron_variant	Intron 1 of 17	ENST00000630721.3	NP_001366039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A6	ENST00000370695.8	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 16	1		ENSP00000359729.4
SLC9A6	ENST00000370698.7	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 16	1		ENSP00000359732.3
SLC9A6	ENST00000630721.3	c.-57+26A>C		intron_variant	Intron 1 of 17	4	NM_001379110.1	ENSP00000487486.2
SLC9A6	ENST00000370701.6	c.-57+26A>C		intron_variant	Intron 1 of 16	1		ENSP00000359735.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982421 Hom.: 0 Cov.: 29 AF XY: 0.00000324 AC XY: 1 AN XY: 308303

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000391

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.091	.;T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.92	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.27
Sift	Benign	0.11	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0040	B;B
Vest4		0.86
MutPred		0.83		Gain of stability (P = 0.1523);Gain of stability (P = 0.1523);
MVP		0.96
ClinPred		0.90	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.33
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-135067662;