14-57589432-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000554729.5(SLC35F4):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,846 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SLC35F4
ENST00000554729.5 start_lost
ENST00000554729.5 start_lost
Scores
19
Clinical Significance
Conservation
PhyloP100: 2.89
Genes affected
SLC35F4 (HGNC:19845): (solute carrier family 35 member F4) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC35F4 | NM_001306087.2 | c.371T>C | p.Met124Thr | missense_variant | 3/8 | ENST00000556826.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC35F4 | ENST00000556826.6 | c.371T>C | p.Met124Thr | missense_variant | 3/8 | 5 | NM_001306087.2 | P1 | |
ENST00000647916.1 | n.872+7917A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248906Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135062
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727086
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
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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 | Jul 19, 2022 | The c.368T>C (p.M123T) alteration is located in exon 3 (coding exon 3) of the SLC35F4 gene. This alteration results from a T to C substitution at nucleotide position 368, causing the methionine (M) at amino acid position 123 to be replaced by a threonine (T). 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
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
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