chr16-55695212-T-C

Position:

• chr16-55695212-T-C

Variant summary

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

The NM_001172501.3(SLC6A2):​c.1023-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,600,988 control chromosomes in the GnomAD database, including 186,087 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 0.45 (16195 hom., cov: 34)
  • Exomes 𝑓: 0.48 (169892 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.1023-66T>C		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.1023-66T>C		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68953 AN: 151956 Hom.: 16190 Cov.: 34

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.480 AC: 695337 AN: 1448914 Hom.: 169892 AF XY: 0.483 AC XY: 348403 AN XY: 721580

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.454 AC: 68976 AN: 152074 Hom.: 16195 Cov.: 34 AF XY: 0.456 AC XY: 33882 AN XY: 74324

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.486

Alfa AF: 0.457 Hom.: 2623

Bravo AF: 0.453

Asia WGS AF: 0.604 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.47

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: rs2279805; hg19: chr16-55729124;