17-30196364-A-AT

Position:

• chr17-30196364-A-AT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001045.6(SLC6A4):​c.*2091_*2092insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0079 in 145,902 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 1153 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*2091_*2092insA		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.*2091_*2092insA		3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.*2091_*2092insA		3_prime_UTR_variant	15/15	1		ENSP00000261707	P1
SLC6A4	ENST00000401766.6	c.*2091_*2092insA		3_prime_UTR_variant	14/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.00789 AC: 1151 AN: 145850 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00541

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.00495

Gnomad SAS AF: 0.00237

Gnomad FIN AF: 0.00156

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.00598

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 92 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52

Gnomad4 EAS exome AF: 0.00

GnomAD4 genome AF: 0.00790 AC: 1153 AN: 145902 Hom.: 3 Cov.: 32 AF XY: 0.00764 AC XY: 541 AN XY: 70838

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.00547

Gnomad4 ASJ AF: 0.00119

Gnomad4 EAS AF: 0.00497

Gnomad4 SAS AF: 0.00238

Gnomad4 FIN AF: 0.00156

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.00643

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;