rs1553175089
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_003047.5(SLC9A1):c.1351A>C(p.Ile451Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. I451I) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC9A1
NM_003047.5 missense
NM_003047.5 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 5.07
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 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SLC9A1
PP5
?
Variant 1-27106019-T-G is Pathogenic according to our data. Variant chr1-27106019-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 520778.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC9A1 | NM_003047.5 | c.1351A>C | p.Ile451Leu | missense_variant | 5/12 | ENST00000263980.8 | |
SLC9A1 | XM_011542021.4 | c.1021A>C | p.Ile341Leu | missense_variant | 6/13 | ||
SLC9A1 | XM_047428769.1 | c.1021A>C | p.Ile341Leu | missense_variant | 9/16 | ||
SLC9A1 | NR_046474.2 | n.1681A>C | non_coding_transcript_exon_variant | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC9A1 | ENST00000263980.8 | c.1351A>C | p.Ile451Leu | missense_variant | 5/12 | 1 | NM_003047.5 | P1 | |
SLC9A1 | ENST00000374086.3 | c.1351A>C | p.Ile451Leu | missense_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 02, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
T;D
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at I451 (P = 0.0129);Gain of catalytic residue at I451 (P = 0.0129);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at