rs3819252

Variant names:

• chr11-20627858-G-A
• rs3819252
• NM_004211.5:c.1396-122G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-20627858-G-A
• chr11-20627858-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004211.5(SLC6A5):​c.1396-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 739,806 control chromosomes in the GnomAD database, including 43,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8133 hom., cov: 31)
  • Exomes 𝑓: 0.34 (35366 hom.)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07
• Publications: 4 publications found

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]

SLC6A5 Gene-Disease associations (from GenCC):

• hyperekplexia 3

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297872 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-20627858-G-A is Benign according to our data. Variant chr11-20627858-G-A is described in ClinVar as Benign. ClinVar VariationId is 1228502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	NM_004211.5	MANE Select	c.1396-122G>A		intron	N/A	NP_004202.4	Q9Y345-1
	SLC6A5	NM_001318369.2		c.694-122G>A		intron	N/A	NP_001305298.1	Q9Y345-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	ENST00000525748.6	TSL:1 MANE Select	c.1396-122G>A		intron	N/A	ENSP00000434364.2	Q9Y345-1
	SLC6A5	ENST00000298923.11	TSL:1	n.*693-122G>A		intron	N/A	ENSP00000298923.7	J3KNC4
	ENSG00000297872	ENST00000751475.1		n.439C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48527 AN: 151730 Hom.: 8130 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.343 AC: 201467 AN: 587958 Hom.: 35366 AF XY: 0.341 AC XY: 108457 AN XY: 318240

African (AFR) AF: 0.235 AC: 3907 AN: 16608

American (AMR) AF: 0.256 AC: 9232 AN: 36096

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 8439 AN: 20188

East Asian (EAS) AF: 0.292 AC: 9739 AN: 33384

South Asian (SAS) AF: 0.255 AC: 16545 AN: 64938

European-Finnish (FIN) AF: 0.343 AC: 13949 AN: 40642

Middle Eastern (MID) AF: 0.384 AC: 957 AN: 2490

European-Non Finnish (NFE) AF: 0.373 AC: 127515 AN: 341980

Other (OTH) AF: 0.354 AC: 11184 AN: 31632

GnomAD4 genome AF: 0.320 AC: 48536 AN: 151848 Hom.: 8133 Cov.: 31 AF XY: 0.319 AC XY: 23639 AN XY: 74190

African (AFR) AF: 0.221 AC: 9147 AN: 41388

American (AMR) AF: 0.337 AC: 5142 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1506 AN: 5150

South Asian (SAS) AF: 0.255 AC: 1221 AN: 4796

European-Finnish (FIN) AF: 0.345 AC: 3630 AN: 10526

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25258 AN: 67940

Other (OTH) AF: 0.347 AC: 731 AN: 2104

Alfa AF: 0.351 Hom.: 39169

Bravo AF: 0.314

Asia WGS AF: 0.269 AC: 939 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.51
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3819252; hg19: chr11-20649404; COSMIC: COSV54234435; COSMIC: COSV54234435;