17-30196068-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001045.6(SLC6A4):​c.*2388C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 151,452 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 161 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLC6A4
NM_001045.6 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.622
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 17-30196068-G-A is Benign according to our data. Variant chr17-30196068-G-A is described in ClinVar as [Benign]. Clinvar id is 891371.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A4NM_001045.6 linkuse as main transcriptc.*2388C>T 3_prime_UTR_variant 15/15 ENST00000650711.1 NP_001036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A4ENST00000650711.1 linkuse as main transcriptc.*2388C>T 3_prime_UTR_variant 15/15 NM_001045.6 ENSP00000498537 P1P31645-1
SLC6A4ENST00000261707.7 linkuse as main transcriptc.*2388C>T 3_prime_UTR_variant 15/151 ENSP00000261707 P1P31645-1
SLC6A4ENST00000401766.6 linkuse as main transcriptc.*2388C>T 3_prime_UTR_variant 14/145 ENSP00000385822 P1P31645-1

Frequencies

GnomAD3 genomes
AF:
0.0270
AC:
4091
AN:
151332
Hom.:
160
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0942
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00914
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000949
Gnomad MID
AF:
0.0129
Gnomad NFE
AF:
0.000516
Gnomad OTH
AF:
0.0193
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 NFE exome
AF:
0.00
GnomAD4 genome
AF:
0.0271
AC:
4099
AN:
151452
Hom.:
161
Cov.:
32
AF XY:
0.0255
AC XY:
1888
AN XY:
74052
show subpopulations
Gnomad4 AFR
AF:
0.0941
Gnomad4 AMR
AF:
0.00912
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000949
Gnomad4 NFE
AF:
0.000516
Gnomad4 OTH
AF:
0.0191
Alfa
AF:
0.0211
Hom.:
12
Bravo
AF:
0.0305
Asia WGS
AF:
0.00549
AC:
19
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Behavior disorder Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.55
DANN
Benign
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56030551; hg19: chr17-28523086; API