rs1042173

Variant names:

• chr17-30197993-A-C
• rs1042173
• NM_001045.6:c.*463T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-30197993-A-C
• chr17-30197993-A-G
• chr17-30197993-A-T

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.*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
• Publications: 132 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: Benign. The variant received -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 VariationId 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.

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.*463T>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.*463T>G		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.*463T>G		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000579221.5	TSL:1	n.*780T>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000463172.1	J3QKP3

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

African (AFR) AF: 0.209 AC: 49 AN: 234

American (AMR) AF: 0.543 AC: 89 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 132 AN: 224

East Asian (EAS) AF: 0.668 AC: 266 AN: 398

South Asian (SAS) AF: 0.518 AC: 29 AN: 56

European-Finnish (FIN) AF: 0.426 AC: 327 AN: 768

Middle Eastern (MID) AF: 0.538 AC: 14 AN: 26

European-Non Finnish (NFE) AF: 0.442 AC: 1659 AN: 3750

Other (OTH) AF: 0.489 AC: 171 AN: 350

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

African (AFR) AF: 0.230 AC: 9562 AN: 41484

American (AMR) AF: 0.507 AC: 7750 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4227 AN: 5176

South Asian (SAS) AF: 0.531 AC: 2561 AN: 4820

European-Finnish (FIN) AF: 0.439 AC: 4640 AN: 10578

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30685 AN: 67936

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.450 Hom.: 51438

Bravo AF: 0.415

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.59
CADD	Benign	9.8
DANN	Benign	0.49
PhyloP100		0.80
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: rs1042173; hg19: chr17-28525011;