NM_001045.6:c.343+1299A>G

Variant names:

• chr17-30220317-T-C
• rs11080122
• NM_001045.6:c.343+1299A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001045.6(SLC6A4):​c.343+1299A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,130 control chromosomes in the GnomAD database, including 49,441 homozygotes. 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 0.81 (49441 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.343+1299A>G		intron_variant	Intron 3 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.343+1299A>G		intron_variant	Intron 3 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.343+1299A>G		intron_variant	Intron 3 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.343+1299A>G		intron_variant	Intron 3 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.343+1299A>G		intron_variant	Intron 2 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122487 AN: 152012 Hom.: 49415 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122566 AN: 152130 Hom.: 49441 Cov.: 31 AF XY: 0.808 AC XY: 60109 AN XY: 74374

African (AFR) AF: 0.757 AC: 31366 AN: 41452

American (AMR) AF: 0.839 AC: 12842 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4666 AN: 5178

South Asian (SAS) AF: 0.825 AC: 3984 AN: 4828

European-Finnish (FIN) AF: 0.819 AC: 8671 AN: 10590

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55398 AN: 68002

Other (OTH) AF: 0.800 AC: 1688 AN: 2110

Alfa AF: 0.812 Hom.: 64516

Bravo AF: 0.806

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.58
PhyloP100		-0.11
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

Other links and lift over

dbSNP: rs11080122; hg19: chr17-28547335;