5-1394407-CGGGAGCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001044.5(SLC6A3):c.*321_*327del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 495,176 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (18 hom., cov: 32)
  • Exomes 𝑓: 0.012 (44 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-1394407-CGGGAGCA-C is Benign according to our data. Variant chr5-1394407-CGGGAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1181229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1532/152146) while in subpopulation NFE AF= 0.0152 (1033/67980). AF 95% confidence interval is 0.0144. There are 18 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.*321_*327del		3_prime_UTR_variant	15/15	ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*321_*327del		3_prime_UTR_variant	15/15	1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.565_571del		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1532 AN: 152028 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0123 AC: 4215 AN: 343030 Hom.: 44 AF XY: 0.0124 AC XY: 2224 AN XY: 179974

Gnomad4 AFR exome AF: 0.00408

Gnomad4 AMR exome AF: 0.00459

Gnomad4 ASJ exome AF: 0.00758

Gnomad4 EAS exome AF: 0.000305

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.0101 AC: 1532 AN: 152146 Hom.: 18 Cov.: 32 AF XY: 0.00979 AC XY: 728 AN XY: 74368

Gnomad4 AFR AF: 0.00308

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00290 Hom.: 0

Bravo AF: 0.00851

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs371613676; hg19: chr5-1394522;