5-1394407-CGGGAGCA-CGGGAGCAGGGAGCA

Variant names:

• chr5-1394407-C-CGGGAGCA
• rs371613676
• NM_001044.5:c.*321_*327dupTGCTCCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001044.5(SLC6A3):​c.*321_*327dupTGCTCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 495,230 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000151 (23/152150) while in subpopulation SAS AF= 0.000415 (2/4824). AF 95% confidence interval is 0.000159. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.*321_*327dupTGCTCCC		3_prime_UTR_variant	Exon 15 of 15	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.*321_*327dupTGCTCCC		3_prime_UTR_variant	Exon 15 of 15	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000512002.2	n.565_571dupTGCTCCC		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000324 AC: 111 AN: 343080 Hom.: 0 Cov.: 0 AF XY: 0.000306 AC XY: 55 AN XY: 179996

Gnomad4 AFR exome AF: 0.0000995

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000131

Gnomad4 SAS exome AF: 0.000405

Gnomad4 FIN exome AF: 0.000256

Gnomad4 NFE exome AF: 0.000372

Gnomad4 OTH exome AF: 0.000305

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74370

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000219

ClinVar

Not reported in ClinVar

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;