19-14951411-T-G

Variant names:

• chr19-14951411-T-G
• rs10414225
• NM_005071.3:c.1500-1021A>C

Variant summary

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

The NM_005071.3(SLC1A6):​c.1500-1021A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,898 control chromosomes in the GnomAD database, including 25,817 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 0.58 (25817 hom., cov: 31)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A6	NM_005071.3	MANE Select	c.1500-1021A>C		intron	N/A	NP_005062.1
	SLC1A6	NM_001384669.1		c.1500-1021A>C		intron	N/A	NP_001371598.1
	SLC1A6	NR_073589.2		n.1461-1021A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A6	ENST00000594383.2	TSL:2 MANE Select	c.1500-1021A>C		intron	N/A	ENSP00000472133.2
	SLC1A6	ENST00000221742.7	TSL:1	c.1500-1021A>C		intron	N/A	ENSP00000221742.3
	SLC1A6	ENST00000600144.5	TSL:1	c.1266-1021A>C		intron	N/A	ENSP00000471038.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88186 AN: 151780 Hom.: 25794 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 88258 AN: 151898 Hom.: 25817 Cov.: 31 AF XY: 0.585 AC XY: 43443 AN XY: 74228

African (AFR) AF: 0.509 AC: 21066 AN: 41406

American (AMR) AF: 0.584 AC: 8916 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1564 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3085 AN: 5158

South Asian (SAS) AF: 0.670 AC: 3227 AN: 4820

European-Finnish (FIN) AF: 0.657 AC: 6934 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41575 AN: 67930

Other (OTH) AF: 0.555 AC: 1167 AN: 2104

Alfa AF: 0.593 Hom.: 72903

Bravo AF: 0.568

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.76
PhyloP100		-1.5
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: rs10414225; hg19: chr19-15062223;