Genetic Variant SLC1A6:c.549-93A>G (chr19-14964454-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.775

Publications

9 publications found

Variant links:

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]

SLC1A6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A6	NM_005071.3	MANE Select	c.549-93A>G	intron	N/A	NP_005062.1	P48664-1
SLC1A6	NM_001384669.1		c.549-93A>G	intron	N/A	NP_001371598.1	P48664-1
SLC1A6	NM_001272087.2		c.549-93A>G	intron	N/A	NP_001259016.1	P48664-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A6	ENST00000594383.2	TSL:2 MANE Select	c.549-93A>G	intron	N/A	ENSP00000472133.2	P48664-1
SLC1A6	ENST00000221742.7	TSL:1	c.549-93A>G	intron	N/A	ENSP00000221742.3	P48664-1
SLC1A6	ENST00000600144.5	TSL:1	c.549-93A>G	intron	N/A	ENSP00000471038.1	M0R063

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28495

AN:

151970

Hom.:

2979

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0995

AC:

2132

AN:

21436

American (AMR)

AF:

0.247

AC:

10707

AN:

43294

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

2197

AN:

21880

East Asian (EAS)

AF:

0.240

AC:

8788

AN:

36586

South Asian (SAS)

AF:

0.260

AC:

18696

AN:

71998

European-Finnish (FIN)

AF:

0.269

AC:

14062

AN:

52258

Middle Eastern (MID)

AF:

0.102

AC:

458

AN:

4500

European-Non Finnish (NFE)

AF:

0.209

AC:

112353

AN:

538358

Other (OTH)

AF:

0.204

AC:

8057

AN:

39570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6780

13561

20341

27122

33902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2410

4820

7230

9640

12050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.187

AC:

28498

AN:

152090

Hom.:

2978

Cov.:

AF XY:

0.193

AC XY:

14359

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.107

AC:

4449

AN:

41522

American (AMR)

AF:

0.228

AC:

3489

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

356

AN:

3470

East Asian (EAS)

AF:

0.266

AC:

1370

AN:

5160

South Asian (SAS)

AF:

0.274

AC:

1319

AN:

4808

European-Finnish (FIN)

AF:

0.265

AC:

2797

AN:

10570

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14238

AN:

67978

Other (OTH)

AF:

0.178

AC:

374

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1177

2354

3532

4709

5886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

3749

Bravo

AF:

0.181

Asia WGS

AF:

0.290

AC:

1008

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

(source)

DANN

Benign

0.60

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over