NM_001045.6:c.*2192G>C

Variant names:

• chr17-30196264-C-G
• rs200532365
• NM_001045.6:c.*2192G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001045.6(SLC6A4):​c.*2192G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 150,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.00050 (0 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964
• 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):

• obsessive-compulsive disorder

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High AC in GnomAd4 at 75 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.*2192G>C		3_prime_UTR	Exon 15 of 15	NP_001036.1	P31645-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.*2192G>C		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.*2192G>C		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000401766.6	TSL:5	c.*2192G>C		3_prime_UTR	Exon 14 of 14	ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes AF: 0.000498 AC: 75 AN: 150728 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000484

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000497 AC: 75 AN: 150828 Hom.: 0 Cov.: 32 AF XY: 0.000421 AC XY: 31 AN XY: 73644

African (AFR) AF: 0.00160 AC: 66 AN: 41152

American (AMR) AF: 0.000329 AC: 5 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67772

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000712 Hom.: 0

Bravo AF: 0.000536

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Behavior disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.57
PhyloP100		0.96

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: rs200532365; hg19: chr17-28523282;