rs745927136
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_003047.5(SLC9A1):c.1585C>T(p.His529Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
SLC9A1
NM_003047.5 missense
NM_003047.5 missense
Scores
4
12
3
Clinical Significance
Conservation
PhyloP100: 9.95
Genes affected
SLC9A1 (HGNC:11071): (solute carrier family 9 member A1) This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SLC9A1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC9A1 | NM_003047.5 | c.1585C>T | p.His529Tyr | missense_variant | 7/12 | ENST00000263980.8 | |
SLC9A1 | XM_011542021.4 | c.1255C>T | p.His419Tyr | missense_variant | 8/13 | ||
SLC9A1 | XM_047428769.1 | c.1255C>T | p.His419Tyr | missense_variant | 11/16 | ||
SLC9A1 | NR_046474.2 | n.1915C>T | non_coding_transcript_exon_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC9A1 | ENST00000263980.8 | c.1585C>T | p.His529Tyr | missense_variant | 7/12 | 1 | NM_003047.5 | P1 | |
SLC9A1 | ENST00000374089.5 | n.810C>T | non_coding_transcript_exon_variant | 2/7 | 2 | ||||
SLC9A1 | ENST00000447808.1 | n.62C>T | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250210Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135468
GnomAD3 exomes
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10
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250210
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135468
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461328Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 726944
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 02, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 529 of the SLC9A1 protein (p.His529Tyr). This variant is present in population databases (rs745927136, gnomAD 0.03%). This missense change has been observed in individual(s) with a neuromuscular disorder (PMID: 30018422). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of catalytic residue at L531 (P = 0.0596);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at