chr16-55703744-G-A

Variant names:

• chr16-55703744-G-A
• rs42460
• NM_001172501.3:c.*1398G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

SLC6A2 Gene-Disease associations (from GenCC):

• postural orthostatic tachycardia syndrome

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	NM_001172501.3	MANE Select	c.*1398G>A		3_prime_UTR	Exon 15 of 15	NP_001165972.1
	SLC6A2	NM_001043.3		c.*1398G>A		3_prime_UTR	Exon 14 of 14	NP_001034.1
	SLC6A2	NM_001172502.1		c.*1398G>A		3_prime_UTR	Exon 12 of 12	NP_001165973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000568943.6	TSL:1 MANE Select	c.*1398G>A		3_prime_UTR	Exon 15 of 15	ENSP00000457473.1
	SLC6A2	ENST00000379906.6	TSL:1	c.*1398G>A		3_prime_UTR	Exon 14 of 14	ENSP00000369237.2
	SLC6A2	ENST00000682050.1		n.*1951G>A		non_coding_transcript_exon	Exon 13 of 13	ENSP00000508367.1

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

African (AFR) AF: 0.916 AC: 14461 AN: 15782

American (AMR) AF: 0.894 AC: 880 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 4838 AN: 5152

East Asian (EAS) AF: 0.799 AC: 2901 AN: 3632

South Asian (SAS) AF: 0.898 AC: 14781 AN: 16456

European-Finnish (FIN) AF: 0.914 AC: 254 AN: 278

Middle Eastern (MID) AF: 0.885 AC: 1434 AN: 1620

European-Non Finnish (NFE) AF: 0.912 AC: 694740 AN: 761738

Other (OTH) AF: 0.900 AC: 24572 AN: 27292

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

African (AFR) AF: 0.913 AC: 37906 AN: 41514

American (AMR) AF: 0.913 AC: 13965 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3191 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4168 AN: 5158

South Asian (SAS) AF: 0.901 AC: 4343 AN: 4820

European-Finnish (FIN) AF: 0.889 AC: 9416 AN: 10594

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61896 AN: 67998

Other (OTH) AF: 0.899 AC: 1899 AN: 2112

Alfa AF: 0.906 Hom.: 52213

Bravo AF: 0.905

Asia WGS AF: 0.855 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.72
PhyloP100		0.044
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs42460; hg19: chr16-55737656;