chr11-20599683-T-C

Variant names:

• chr11-20599683-T-C
• NM_004211.5:c.3+8T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004211.5(SLC6A5):​c.3+8T>C variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A5 NM_004211.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

Genes affected

SLC6A5 (HGNC:11051): (solute carrier family 6 member 5) This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.3+8T>C		splice_region_variant, intron_variant	Intron 1 of 15	ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.-561+8T>C		splice_region_variant, intron_variant	Intron 1 of 14		NP_001305298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.3+8T>C		splice_region_variant, intron_variant	Intron 1 of 15	1	NM_004211.5	ENSP00000434364.2
SLC6A5	ENST00000298923.11	n.3+8T>C		splice_region_variant, intron_variant	Intron 1 of 14	1		ENSP00000298923.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0020
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-20621229;