chr17-30196364-AT-A

Position:

• chr17-30196364-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001045.6(SLC6A4):​c.*2091del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 145,752 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (7 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.516

Genes affected

SLC6A4 (HGNC:11050): (solute carrier family 6 member 4) This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*2091del		3_prime_UTR_variant	15/15	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.*2091del		3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.*2091del		3_prime_UTR_variant	15/15	1		ENSP00000261707	P1
SLC6A4	ENST00000401766.6	c.*2091del		3_prime_UTR_variant	14/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1095 AN: 145614 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00507

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.000595

Gnomad SAS AF: 0.00216

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0100

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.00752

GnomAD4 exome AF: 0.100 AC: 9 AN: 90 Hom.: 0 Cov.: 0 AF XY: 0.0600 AC XY: 3 AN XY: 50

Gnomad4 EAS exome AF: 0.100

GnomAD4 genome AF: 0.00754 AC: 1098 AN: 145662 Hom.: 7 Cov.: 32 AF XY: 0.00802 AC XY: 567 AN XY: 70708

Gnomad4 AFR AF: 0.00835

Gnomad4 AMR AF: 0.00507

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.000596

Gnomad4 SAS AF: 0.00217

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.00552

Gnomad4 OTH AF: 0.00746

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Behavior disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs748194758; hg19: chr17-28523382;