rs1042173

Positions:

• chr17-30197993-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001045.6(SLC6A4):​c.*463T>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 0.415 in 158,042 control chromosomes in the GnomAD database, including 15,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14459 hom., cov: 32)
  • Exomes 𝑓: 0.46 (652 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.803

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-30197993-A-C is Benign according to our data. Variant chr17-30197993-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 322521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*463T>G		3_prime_UTR_variant	15/15	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.*463T>G		3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.*463T>G		3_prime_UTR_variant	15/15	1		ENSP00000261707	P1
SLC6A4	ENST00000579221.5	c.*780T>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000463172
SLC6A4	ENST00000401766.6	c.*463T>G		3_prime_UTR_variant	14/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62830 AN: 151952 Hom.: 14461 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.458 AC: 2736 AN: 5970 Hom.: 652 Cov.: 0 AF XY: 0.448 AC XY: 1404 AN XY: 3134

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.442

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.413 AC: 62831 AN: 152072 Hom.: 14459 Cov.: 32 AF XY: 0.422 AC XY: 31348 AN XY: 74348

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.447

Alfa AF: 0.461 Hom.: 22280

Bravo AF: 0.415

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Behavior disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.8
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1042173; hg19: chr17-28525011;