17-30215528-G-T

Variant names:

• chr17-30215528-G-T
• rs28914829
• NM_001045.6:c.1076+83C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001045.6(SLC6A4):​c.1076+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 985,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 0 publications found

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]

SLC6A4 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.1076+83C>A		intron	N/A	NP_001036.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.1076+83C>A		intron	N/A	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.1076+83C>A		intron	N/A	ENSP00000261707.3
	SLC6A4	ENST00000394821.2	TSL:1	c.1076+83C>A		intron	N/A	ENSP00000378298.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000203 AC: 2 AN: 985756 Hom.: 0 AF XY: 0.00000392 AC XY: 2 AN XY: 510392

African (AFR) AF: 0.00 AC: 0 AN: 24226

American (AMR) AF: 0.00 AC: 0 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22794

East Asian (EAS) AF: 0.00 AC: 0 AN: 37582

South Asian (SAS) AF: 0.00 AC: 0 AN: 76046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52672

Middle Eastern (MID) AF: 0.000205 AC: 1 AN: 4874

European-Non Finnish (NFE) AF: 0.00000147 AC: 1 AN: 679088

Other (OTH) AF: 0.00 AC: 0 AN: 44648

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		0.14

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

Other links and lift over

dbSNP: rs28914829; hg19: chr17-28542546;