rs3803927

Positions:

• chr19-14964454-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005071.3(SLC1A6):​c.549-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 981,970 control chromosomes in the GnomAD database, including 23,399 homozygotes. 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: 𝑓 0.19 (2978 hom., cov: 31)
  • Exomes 𝑓: 0.21 (20421 hom.)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A6	NM_005071.3	c.549-93A>G		intron_variant		ENST00000594383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A6	ENST00000594383.2	c.549-93A>G		intron_variant		2	NM_005071.3	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28495 AN: 151970 Hom.: 2979 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.214 AC: 177450 AN: 829880 Hom.: 20421 AF XY: 0.216 AC XY: 94163 AN XY: 436868

Gnomad4 AFR exome AF: 0.0995

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.187 AC: 28498 AN: 152090 Hom.: 2978 Cov.: 31 AF XY: 0.193 AC XY: 14359 AN XY: 74330

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.178

Alfa AF: 0.202 Hom.: 2708

Bravo AF: 0.181

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.60

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: rs3803927; hg19: chr19-15075266; COSMIC: COSV55673873; COSMIC: COSV55673873;