rs42460

Positions:

• chr16-55703744-G-A
• chr16-55703744-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172501.3(SLC6A2):​c.*1398G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 985,112 control chromosomes in the GnomAD database, including 408,151 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 0.91 (62433 hom., cov: 31)
  • Exomes 𝑓: 0.91 (345718 hom.)
• Consequence: SLC6A2 NM_001172501.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

Genes affected

SLC6A2 (HGNC:11048): (solute carrier family 6 member 2) This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.*1398G>A		3_prime_UTR_variant	15/15	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.*1398G>A		3_prime_UTR_variant	15/15	1	NM_001172501.3	ENSP00000457473	P1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137724 AN: 152060 Hom.: 62380 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.911 AC: 758861 AN: 832934 Hom.: 345718 Cov.: 32 AF XY: 0.911 AC XY: 350609 AN XY: 384658

Gnomad4 AFR exome AF: 0.916

Gnomad4 AMR exome AF: 0.894

Gnomad4 ASJ exome AF: 0.939

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.898

Gnomad4 FIN exome AF: 0.914

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.906 AC: 137836 AN: 152178 Hom.: 62433 Cov.: 31 AF XY: 0.904 AC XY: 67276 AN XY: 74406

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.899

Alfa AF: 0.907 Hom.: 31279

Bravo AF: 0.905

Asia WGS AF: 0.855 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs42460; hg19: chr16-55737656;