rs13384641

Variant names:

• chr2-107987962-C-A
• rs13384641
• NM_021815.5:c.-51-143C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-107987962-C-A
• chr2-107987962-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021815.5(SLC5A7):​c.-51-143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 272,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: SLC5A7 NM_021815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A7	NM_021815.5	c.-51-143C>A		intron_variant	Intron 1 of 8	ENST00000264047.3	NP_068587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A7	ENST00000264047.3	c.-51-143C>A		intron_variant	Intron 1 of 8	1	NM_021815.5	ENSP00000264047.2
SLC5A7	ENST00000409059.5	c.-48-146C>A		intron_variant	Intron 1 of 8	1		ENSP00000387346.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000366 AC: 1 AN: 272884 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 140086

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9380

American (AMR) AF: 0.00 AC: 0 AN: 11320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9438

East Asian (EAS) AF: 0.00 AC: 0 AN: 24532

South Asian (SAS) AF: 0.00 AC: 0 AN: 9846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1360

European-Non Finnish (NFE) AF: 0.00000589 AC: 1 AN: 169846

Other (OTH) AF: 0.00 AC: 0 AN: 17254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.83
DANN	Benign	0.41
PhyloP100		-0.65

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: rs13384641; hg19: chr2-108604418;