rs2872524
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP6BS2
The NM_005629.4(SLC6A8):c.1714G>A(p.Val572Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,094,605 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V572V) has been classified as Likely benign.
Frequency
Consequence
NM_005629.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.1714G>A | p.Val572Met | missense_variant | 12/13 | ENST00000253122.10 | |
SLC6A8 | NM_001142805.2 | c.1684G>A | p.Val562Met | missense_variant | 12/13 | ||
SLC6A8 | NM_001142806.1 | c.1369G>A | p.Val457Met | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.1714G>A | p.Val572Met | missense_variant | 12/13 | 1 | NM_005629.4 | P1 | |
SLC6A8 | ENST00000430077.6 | c.1369G>A | p.Val457Met | missense_variant | 12/13 | 2 | |||
SLC6A8 | ENST00000485324.1 | n.2021G>A | non_coding_transcript_exon_variant | 5/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 exomes AF: 0.0000397 AC: 7AN: 176255Hom.: 0 AF XY: 0.0000481 AC XY: 3AN XY: 62357
GnomAD4 exome AF: 0.0000393 AC: 43AN: 1094605Hom.: 0 Cov.: 38 AF XY: 0.0000388 AC XY: 14AN XY: 360917
GnomAD4 genome ? Cov.: 25
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 07, 2017 | A variant of uncertain significance has been identified in the SLC6A8 gene. The V572M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V572M variant is observed in 6/35470 (0.02%) alleles from individuals of European background, including 3 unrelated hemizygous individuals in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V572M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However. in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Creatine transporter deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at