chr11-93148820-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_152313.4(SLC36A4):c.1232G>A(p.Arg411His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
SLC36A4
NM_152313.4 missense
NM_152313.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 2.95
Genes affected
SLC36A4 (HGNC:19660): (solute carrier family 36 member 4) SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).[supplied by OMIM, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36700034).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC36A4 | NM_152313.4 | c.1232G>A | p.Arg411His | missense_variant | 11/11 | ENST00000326402.9 | |
SLC36A4 | NM_001286139.2 | c.827G>A | p.Arg276His | missense_variant | 11/11 | ||
SLC36A4 | XM_047426350.1 | c.1175G>A | p.Arg392His | missense_variant | 11/11 | ||
SLC36A4 | XM_047426351.1 | c.914G>A | p.Arg305His | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC36A4 | ENST00000326402.9 | c.1232G>A | p.Arg411His | missense_variant | 11/11 | 1 | NM_152313.4 | P1 | |
SLC36A4 | ENST00000529184.5 | c.827G>A | p.Arg276His | missense_variant | 11/11 | 2 | |||
SLC36A4 | ENST00000527503.1 | n.1406G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151914Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248228Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134228
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1459254Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 725870
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151914Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74184
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.1232G>A (p.R411H) alteration is located in exon 11 (coding exon 11) of the SLC36A4 gene. This alteration results from a G to A substitution at nucleotide position 1232, causing the arginine (R) at amino acid position 411 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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