chr5-1394500-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001044.5(SLC6A3):​c.*235G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 634,504 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 20 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

SLC6A3
NM_001044.5 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.941
Variant links:
Genes affected
SLC6A3 (HGNC:11049): (solute carrier family 6 member 3) This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3' UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.[provided by RefSeq, Nov 2009]

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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=-0.77).
BP6
Variant 5-1394500-C-T is Benign according to our data. Variant chr5-1394500-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1215152.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00866 (1318/152278) while in subpopulation AFR AF= 0.0295 (1224/41546). AF 95% confidence interval is 0.0281. There are 20 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC6A3NM_001044.5 linkuse as main transcriptc.*235G>A 3_prime_UTR_variant 15/15 ENST00000270349.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A3ENST00000270349.12 linkuse as main transcriptc.*235G>A 3_prime_UTR_variant 15/151 NM_001044.5 P1
SLC6A3ENST00000512002.2 linkuse as main transcriptn.479G>A non_coding_transcript_exon_variant 3/31

Frequencies

GnomAD3 genomes
AF:
0.00864
AC:
1315
AN:
152160
Hom.:
20
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0295
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.0105
GnomAD4 exome
AF:
0.00113
AC:
544
AN:
482226
Hom.:
5
Cov.:
3
AF XY:
0.000949
AC XY:
243
AN XY:
256140
show subpopulations
Gnomad4 AFR exome
AF:
0.0291
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000199
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000603
Gnomad4 OTH exome
AF:
0.00211
GnomAD4 genome
AF:
0.00866
AC:
1318
AN:
152278
Hom.:
20
Cov.:
33
AF XY:
0.00814
AC XY:
606
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0295
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00573
Hom.:
4
Bravo
AF:
0.00992
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
7.2
DANN
Benign
0.83

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: rs28363167; hg19: chr5-1394615; API