rs333226

Variant names:

• chr2-108011461-G-A
• rs333226
• NM_021815.5:c.*600G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-108011461-G-A
• chr2-108011461-G-C
• chr2-108011461-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021815.5(SLC5A7):​c.*600G>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 0.906 in 152,232 control chromosomes in the GnomAD database, including 62,743 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 (62743 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC5A7 NM_021815.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 2 publications found

Genes affected

SLC5A7 (HGNC:14025): (solute carrier family 5 member 7) This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

SLC5A7 Gene-Disease associations (from GenCC):

• neuronopathy, distal hereditary motor, type 7A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 20

  Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• distal hereditary motor neuropathy type 7

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021815.5. 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
	SLC5A7	NM_021815.5	MANE Select	c.*600G>A		3_prime_UTR	Exon 9 of 9	NP_068587.1
	SLC5A7	NM_001305005.3		c.*600G>A		3_prime_UTR	Exon 9 of 9	NP_001291934.1
	SLC5A7	NM_001305006.3		c.*600G>A		3_prime_UTR	Exon 8 of 8	NP_001291935.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A7	ENST00000264047.3	TSL:1 MANE Select	c.*600G>A		3_prime_UTR	Exon 9 of 9	ENSP00000264047.2

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137759 AN: 152114 Hom.: 62680 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.888

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.906 AC: 137882 AN: 152232 Hom.: 62743 Cov.: 32 AF XY: 0.910 AC XY: 67724 AN XY: 74432

African (AFR) AF: 0.976 AC: 40565 AN: 41560

American (AMR) AF: 0.914 AC: 13954 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2718 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5144 AN: 5176

South Asian (SAS) AF: 0.874 AC: 4217 AN: 4824

European-Finnish (FIN) AF: 0.948 AC: 10054 AN: 10604

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.858 AC: 58342 AN: 68002

Other (OTH) AF: 0.888 AC: 1880 AN: 2116

Alfa AF: 0.872 Hom.: 73238

Bravo AF: 0.908

Asia WGS AF: 0.938 AC: 3256 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.047
DANN	Benign	0.35
PhyloP100		-3.0
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: rs333226; hg19: chr2-108627917;