chr11-93165935-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152313.4(SLC36A4):c.850T>A(p.Phe284Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,606,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
SLC36A4
NM_152313.4 missense
NM_152313.4 missense
Scores
7
7
5
Clinical Significance
Conservation
PhyloP100: 8.14
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.842
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC36A4 | NM_152313.4 | c.850T>A | p.Phe284Ile | missense_variant | 8/11 | ENST00000326402.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC36A4 | ENST00000326402.9 | c.850T>A | p.Phe284Ile | missense_variant | 8/11 | 1 | NM_152313.4 | P1 | |
SLC36A4 | ENST00000529184.5 | c.445T>A | p.Phe149Ile | missense_variant | 8/11 | 2 | |||
SLC36A4 | ENST00000534116.1 | c.532T>A | p.Phe178Ile | missense_variant | 5/7 | 3 | |||
SLC36A4 | ENST00000526735.1 | n.1596T>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249282Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134866
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GnomAD4 exome AF: 0.0000165 AC: 24AN: 1454716Hom.: 0 Cov.: 29 AF XY: 0.0000152 AC XY: 11AN XY: 723554
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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 | Apr 12, 2023 | The c.850T>A (p.F284I) alteration is located in exon 8 (coding exon 8) of the SLC36A4 gene. This alteration results from a T to A substitution at nucleotide position 850, causing the phenylalanine (F) at amino acid position 284 to be replaced by an isoleucine (I). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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