11-20601059-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004211.5(SLC6A5):c.4-70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,479,216 control chromosomes in the GnomAD database, including 8,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1025 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7051 hom.)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-20601059-A-G is Benign according to our data. Variant chr11-20601059-A-G is described in ClinVar as [Benign]. Clinvar id is 1297945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A5	NM_004211.5	c.4-70A>G		intron_variant		ENST00000525748.6
SLC6A5	NM_001318369.2	c.-560-70A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A5	ENST00000525748.6	c.4-70A>G		intron_variant		1	NM_004211.5	P1
SLC6A5	ENST00000298923.11	c.4-70A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16849 AN: 152154 Hom.: 1023 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0957

GnomAD4 exome AF: 0.0991 AC: 131442 AN: 1326944 Hom.: 7051 AF XY: 0.0982 AC XY: 64473 AN XY: 656478

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0686

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.0595

Gnomad4 FIN exome AF: 0.0576

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.111 AC: 16857 AN: 152272 Hom.: 1025 Cov.: 33 AF XY: 0.106 AC XY: 7871 AN XY: 74462

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00694

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.104 Hom.: 145

Bravo AF: 0.115

Asia WGS AF: 0.0530 AC: 189 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.015
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs72944437; hg19: chr11-20622605;