chr5-1400816-A-ATCTACACCAGCCCTG

Variant names:

• chr5-1400816-A-ATCTACACCAGCCCTG
• rs28363149
• NM_001044.5:c.1839+98_1839+99insCAGGGCTGGTGTAGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001044.5(SLC6A3):​c.1839+98_1839+99insCAGGGCTGGTGTAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 878,280 control chromosomes in the GnomAD database, including 6,878 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (3819 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3059 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123
• Publications: 1 publications found

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]

SLC6A3 Gene-Disease associations (from GenCC):

• classic dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• SLC6A3-related dopamine transporter deficiency syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• parkinsonism-dystonia, infantile

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-1400816-A-ATCTACACCAGCCCTG is Benign according to our data. Variant chr5-1400816-A-ATCTACACCAGCCCTG is described in ClinVar as [Benign]. Clinvar id is 1291957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1839+98_1839+99insCAGGGCTGGTGTAGA		intron_variant	Intron 14 of 14	ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1839+98_1839+99insCAGGGCTGGTGTAGA		intron_variant	Intron 14 of 14	1	NM_001044.5	ENSP00000270349.9
SLC6A3	ENST00000512002.2	n.220+98_220+99insCAGGGCTGGTGTAGA		intron_variant	Intron 2 of 2	1
SLC6A3	ENST00000713696.1	c.*34+98_*34+99insCAGGGCTGGTGTAGA		intron_variant	Intron 14 of 14			ENSP00000519000.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24893 AN: 151866 Hom.: 3800 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.0675 AC: 49002 AN: 726298 Hom.: 3059 AF XY: 0.0674 AC XY: 25733 AN XY: 381768

African (AFR) AF: 0.394 AC: 6920 AN: 17576

American (AMR) AF: 0.0507 AC: 1768 AN: 34844

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 1861 AN: 20988

East Asian (EAS) AF: 0.0249 AC: 815 AN: 32788

South Asian (SAS) AF: 0.0769 AC: 5056 AN: 65716

European-Finnish (FIN) AF: 0.0762 AC: 3591 AN: 47120

Middle Eastern (MID) AF: 0.0643 AC: 284 AN: 4418

European-Non Finnish (NFE) AF: 0.0553 AC: 25812 AN: 467072

Other (OTH) AF: 0.0809 AC: 2895 AN: 35776

GnomAD4 genome AF: 0.164 AC: 24962 AN: 151982 Hom.: 3819 Cov.: 31 AF XY: 0.159 AC XY: 11826 AN XY: 74298

African (AFR) AF: 0.412 AC: 17061 AN: 41382

American (AMR) AF: 0.0775 AC: 1184 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.0219 AC: 113 AN: 5170

South Asian (SAS) AF: 0.0832 AC: 400 AN: 4806

European-Finnish (FIN) AF: 0.0789 AC: 837 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0683 AC: 4644 AN: 67958

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.133 Hom.: 232

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28363149; hg19: chr5-1400931;