chr11-93148839-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152313.4(SLC36A4):c.1213G>A(p.Gly405Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,597,728 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
SLC36A4
NM_152313.4 missense
NM_152313.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 0.573
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0330894).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC36A4 | NM_152313.4 | c.1213G>A | p.Gly405Arg | missense_variant | 11/11 | ENST00000326402.9 | |
SLC36A4 | NM_001286139.2 | c.808G>A | p.Gly270Arg | missense_variant | 11/11 | ||
SLC36A4 | XM_047426350.1 | c.1156G>A | p.Gly386Arg | missense_variant | 11/11 | ||
SLC36A4 | XM_047426351.1 | c.895G>A | p.Gly299Arg | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC36A4 | ENST00000326402.9 | c.1213G>A | p.Gly405Arg | missense_variant | 11/11 | 1 | NM_152313.4 | P1 | |
SLC36A4 | ENST00000529184.5 | c.808G>A | p.Gly270Arg | missense_variant | 11/11 | 2 | |||
SLC36A4 | ENST00000527503.1 | n.1387G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151954Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000153 AC: 36AN: 235332Hom.: 1 AF XY: 0.000196 AC XY: 25AN XY: 127574
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GnomAD4 exome AF: 0.000111 AC: 160AN: 1445658Hom.: 1 Cov.: 31 AF XY: 0.000157 AC XY: 113AN XY: 718810
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74332
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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 | Feb 27, 2023 | The c.1213G>A (p.G405R) 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 1213, causing the glycine (G) at amino acid position 405 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of methylation at G405 (P = 0.0169);.;
MVP
MPC
ClinPred
T
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