chr17-30195008-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001045.6(SLC6A4):c.*3448G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 152,282 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.017 ( 32 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
SLC6A4
NM_001045.6 3_prime_UTR
NM_001045.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.337
Genes affected
SLC6A4 (HGNC:11050): (solute carrier family 6 member 4) This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 17-30195008-C-G is Benign according to our data. Variant chr17-30195008-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 889814.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2591/152282) while in subpopulation NFE AF= 0.0249 (1697/68020). AF 95% confidence interval is 0.024. There are 32 homozygotes in gnomad4. There are 1276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2592 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A4 | NM_001045.6 | c.*3448G>C | 3_prime_UTR_variant | 15/15 | ENST00000650711.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A4 | ENST00000650711.1 | c.*3448G>C | 3_prime_UTR_variant | 15/15 | NM_001045.6 | P1 | |||
SLC6A4 | ENST00000261707.7 | c.*3448G>C | 3_prime_UTR_variant | 15/15 | 1 | P1 | |||
SLC6A4 | ENST00000401766.6 | c.*3448G>C | 3_prime_UTR_variant | 14/14 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0170 AC: 2592AN: 152164Hom.: 32 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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GnomAD4 genome ? AF: 0.0170 AC: 2591AN: 152282Hom.: 32 Cov.: 32 AF XY: 0.0171 AC XY: 1276AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Behavior disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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