19-14972983-C-T

Variant names:

• chr19-14972983-C-T
• rs8103212
• NM_005071.3:c.-7-66G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005071.3(SLC1A6):​c.-7-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,280,364 control chromosomes in the GnomAD database, including 180,485 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 0.53 (21404 hom., cov: 33)
  • Exomes 𝑓: 0.53 (159081 hom.)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005071.3. 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
	SLC1A6	NM_005071.3	MANE Select	c.-7-66G>A		intron	N/A	NP_005062.1	P48664-1
	SLC1A6	NM_001384669.1		c.-7-66G>A		intron	N/A	NP_001371598.1	P48664-1
	SLC1A6	NM_001272087.2		c.-7-66G>A		intron	N/A	NP_001259016.1	P48664-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A6	ENST00000594383.2	TSL:2 MANE Select	c.-7-66G>A		intron	N/A	ENSP00000472133.2	P48664-1
	SLC1A6	ENST00000600144.5	TSL:1	c.-7-66G>A		intron	N/A	ENSP00000471038.1	M0R063
	SLC1A6	ENST00000544886.6	TSL:1	c.-7-66G>A		intron	N/A	ENSP00000446175.1	P48664-2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80099 AN: 151990 Hom.: 21392 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.530 AC: 598150 AN: 1128256 Hom.: 159081 Cov.: 15 AF XY: 0.532 AC XY: 295244 AN XY: 554484

African (AFR) AF: 0.480 AC: 12228 AN: 25464

American (AMR) AF: 0.560 AC: 12980 AN: 23182

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 7232 AN: 18920

East Asian (EAS) AF: 0.684 AC: 23263 AN: 34024

South Asian (SAS) AF: 0.603 AC: 37570 AN: 62324

European-Finnish (FIN) AF: 0.580 AC: 25881 AN: 44586

Middle Eastern (MID) AF: 0.381 AC: 1283 AN: 3366

European-Non Finnish (NFE) AF: 0.521 AC: 452766 AN: 868328

Other (OTH) AF: 0.519 AC: 24947 AN: 48062

GnomAD4 genome AF: 0.527 AC: 80150 AN: 152108 Hom.: 21404 Cov.: 33 AF XY: 0.533 AC XY: 39683 AN XY: 74384

African (AFR) AF: 0.489 AC: 20265 AN: 41474

American (AMR) AF: 0.555 AC: 8482 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1334 AN: 3468

East Asian (EAS) AF: 0.683 AC: 3529 AN: 5170

South Asian (SAS) AF: 0.630 AC: 3040 AN: 4826

European-Finnish (FIN) AF: 0.582 AC: 6168 AN: 10590

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35740 AN: 67974

Other (OTH) AF: 0.491 AC: 1040 AN: 2116

Alfa AF: 0.461 Hom.: 3024

Bravo AF: 0.521

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.81
PhyloP100		-0.86
PromoterAI		-0.028	Neutral
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8103212; hg19: chr19-15083795;