NM_001044.5:c.*1097T>C

Variant names:

• chr5-1393638-A-G
• rs11564775
• NM_001044.5:c.*1097T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001044.5(SLC6A3):​c.*1097T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (18 hom., cov: 0)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: SLC6A3 NM_001044.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 8 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	NM_001044.5	MANE Select	c.*1097T>C		3_prime_UTR	Exon 15 of 15	NP_001035.1	Q01959

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A3	ENST00000270349.12	TSL:1 MANE Select	c.*1097T>C		3_prime_UTR	Exon 15 of 15	ENSP00000270349.9	Q01959

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 3130 AN: 44932 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0929

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0388

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0753

GnomAD4 exome AF: 0.0297 AC: 29 AN: 978 Hom.: 0 Cov.: 0 AF XY: 0.0331 AC XY: 18 AN XY: 544

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 28

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 272

Middle Eastern (MID) AF: 0.0482 AC: 19 AN: 394

European-Non Finnish (NFE) AF: 0.0309 AC: 6 AN: 194

Other (OTH) AF: 0.0517 AC: 3 AN: 58

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0697 AC: 3135 AN: 44962 Hom.: 18 Cov.: 0 AF XY: 0.0686 AC XY: 1538 AN XY: 22416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.102 AC: 1278 AN: 12512

American (AMR) AF: 0.0534 AC: 256 AN: 4790

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 43 AN: 698

East Asian (EAS) AF: 0.0390 AC: 75 AN: 1924

South Asian (SAS) AF: 0.0536 AC: 80 AN: 1492

European-Finnish (FIN) AF: 0.0648 AC: 188 AN: 2900

Middle Eastern (MID) AF: 0.235 AC: 16 AN: 68

European-Non Finnish (NFE) AF: 0.0573 AC: 1127 AN: 19680

Other (OTH) AF: 0.0759 AC: 51 AN: 672

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.338 Hom.: 363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.068
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11564775;

hg19: chr5-1393753;