11-20600983-C-A

Position:

• chr11-20600983-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004211.5(SLC6A5):​c.4-146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 758,616 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (21 hom.)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-20600983-C-A is Benign according to our data. Variant chr11-20600983-C-A is described in ClinVar as [Benign]. Clinvar id is 1269491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.4-146C>A		intron_variant		ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.-560-146C>A		intron_variant			NP_001305298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.4-146C>A		intron_variant		1	NM_004211.5	ENSP00000434364	P1
SLC6A5	ENST00000298923.11	c.4-146C>A		intron_variant, NMD_transcript_variant		1		ENSP00000298923

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2240 AN: 152162 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00133 AC: 805 AN: 606336 Hom.: 21 AF XY: 0.00110 AC XY: 343 AN XY: 312686

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.000139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000642

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000284

Gnomad4 OTH exome AF: 0.00304

GnomAD4 genome AF: 0.0148 AC: 2249 AN: 152280 Hom.: 64 Cov.: 33 AF XY: 0.0142 AC XY: 1056 AN XY: 74462

Gnomad4 AFR AF: 0.0522

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0114 Hom.: 5

Bravo AF: 0.0167

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs76017471; hg19: chr11-20622529;