X-135985514-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001042537.2(SLC9A6):​c.12C>T​(p.Arg4Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 996,677 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. R4R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000020 ( 0 hom. 0 hem. )

Consequence

SLC9A6
NM_001042537.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.375
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP7
Synonymous conserved (PhyloP=0.375 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC9A6NM_001379110.1 linkc.-57+37C>T intron_variant Intron 1 of 17 ENST00000630721.3 NP_001366039.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC9A6ENST00000370695.8 linkc.12C>T p.Arg4Arg synonymous_variant Exon 1 of 16 1 ENSP00000359729.4 Q92581-2
SLC9A6ENST00000370698.7 linkc.12C>T p.Arg4Arg synonymous_variant Exon 1 of 16 1 ENSP00000359732.3 Q92581-1
SLC9A6ENST00000630721.3 linkc.-57+37C>T intron_variant Intron 1 of 17 4 NM_001379110.1 ENSP00000487486.2 A0A0D9SGH0
SLC9A6ENST00000370701.6 linkc.-57+37C>T intron_variant Intron 1 of 16 1 ENSP00000359735.1 Q92581-3

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.0000163
AC:
1
AN:
61388
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
8562
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000201
AC:
2
AN:
996677
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
312285
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000381
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000380
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_noAF
Benign
-0.58
CADD
Benign
16
DANN
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1415889484; hg19: chrX-135067673; API