11-93162757-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152313.4(SLC36A4):c.986T>G(p.Phe329Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 0 hom. )
Consequence
SLC36A4
NM_152313.4 missense
NM_152313.4 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 8.37
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC36A4 | NM_152313.4 | c.986T>G | p.Phe329Cys | missense_variant | 9/11 | ENST00000326402.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC36A4 | ENST00000326402.9 | c.986T>G | p.Phe329Cys | missense_variant | 9/11 | 1 | NM_152313.4 | P1 | |
SLC36A4 | ENST00000529184.5 | c.581T>G | p.Phe194Cys | missense_variant | 9/11 | 2 | |||
SLC36A4 | ENST00000534116.1 | c.668T>G | p.Phe223Cys | missense_variant | 6/7 | 3 | |||
SLC36A4 | ENST00000526735.1 | n.1732T>G | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152226Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000212 AC: 53AN: 250316Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 135286
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GnomAD4 exome AF: 0.000363 AC: 531AN: 1460918Hom.: 0 Cov.: 30 AF XY: 0.000337 AC XY: 245AN XY: 726760
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GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74498
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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 | Dec 06, 2022 | The c.986T>G (p.F329C) alteration is located in exon 9 (coding exon 9) of the SLC36A4 gene. This alteration results from a T to G substitution at nucleotide position 986, causing the phenylalanine (F) at amino acid position 329 to be replaced by a cysteine (C). 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
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
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;T
Polyphen
D;.;.
Vest4
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