chr17-30196103-T-C

Variant names:

• chr17-30196103-T-C
• rs8066731
• NM_001045.6:c.*2353A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001045.6(SLC6A4):​c.*2353A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,896 control chromosomes in the GnomAD database, including 24,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24452 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.283
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-30196103-T-C is Benign according to our data. Variant chr17-30196103-T-C is described in ClinVar as Benign. ClinVar VariationId is 891372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

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.*2353A>G		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.*2353A>G		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.*2353A>G		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000401766.6	TSL:5	c.*2353A>G		3_prime_UTR	Exon 14 of 14	ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84710 AN: 151778 Hom.: 24426 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.565

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.558 AC: 84775 AN: 151896 Hom.: 24452 Cov.: 32 AF XY: 0.562 AC XY: 41687 AN XY: 74240

African (AFR) AF: 0.667 AC: 27601 AN: 41408

American (AMR) AF: 0.577 AC: 8810 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2024 AN: 3466

East Asian (EAS) AF: 0.818 AC: 4246 AN: 5192

South Asian (SAS) AF: 0.556 AC: 2673 AN: 4810

European-Finnish (FIN) AF: 0.451 AC: 4733 AN: 10506

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32904 AN: 67938

Other (OTH) AF: 0.560 AC: 1180 AN: 2106

Alfa AF: 0.513 Hom.: 2421

Bravo AF: 0.574

Asia WGS AF: 0.628 AC: 2186 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Behavior disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		-0.28
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: rs8066731; hg19: chr17-28523121;