rs57098334

chr17-30221568-A-ACAGCCCACCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCchr17-30221568-A-ACAGCCCACCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCchr17-30221568-A-ACAGCCCACCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACCCAGCCCACC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001045.6(SLC6A4):c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A4	NM_001045.6	c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG		intron_variant		ENST00000650711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A4	ENST00000650711.1	c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG		intron_variant			NM_001045.6	P1
SLC6A4	ENST00000261707.7	c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG		intron_variant		1		P1
SLC6A4	ENST00000394821.2	c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG		intron_variant		1
SLC6A4	ENST00000401766.6	c.343+47_343+48insGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGGTGGGCTGGTGGGCTG		intron_variant		5		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57098334; hg19: chr17-28548586;