chr11-35419429-T-A

Variant names:

• chr11-35419429-T-A
• rs4354668
• NM_004171.4:c.-463A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004171.4(SLC1A2):​c.-463A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC1A2 NM_004171.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 33 publications found

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.-463A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	ENST00000278379.9	NP_004162.2
SLC1A2	NM_004171.4	c.-463A>T		5_prime_UTR_variant	Exon 1 of 11	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.-463A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	1	NM_004171.4	ENSP00000278379.3
SLC1A2	ENST00000278379.9	c.-463A>T		5_prime_UTR_variant	Exon 1 of 11	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 29748 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 15358

African (AFR) AF: 0.00 AC: 0 AN: 988

American (AMR) AF: 0.00 AC: 0 AN: 622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1118

East Asian (EAS) AF: 0.00 AC: 0 AN: 2196

South Asian (SAS) AF: 0.00 AC: 0 AN: 436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 144

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 19860

Other (OTH) AF: 0.00 AC: 0 AN: 1896

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		-0.72
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4354668; hg19: chr11-35440976;