Genetic Variant SLC1A6:c.343+137C>G (chr19-14971600-G-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.343+137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 846,028 control chromosomes in the GnomAD database, including 125,727 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 ( 21830 hom., cov: 31)

Exomes 𝑓: 0.54 ( 103897 hom. )

Consequence

SLC1A6
NM_005071.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

Publications

2 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 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.343+137C>G	intron	N/A	NP_005062.1	P48664-1
SLC1A6	NM_001384669.1		c.343+137C>G	intron	N/A	NP_001371598.1	P48664-1
SLC1A6	NM_001272087.2		c.343+137C>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.343+137C>G	intron	N/A	ENSP00000472133.2	P48664-1
SLC1A6	ENST00000221742.7	TSL:1	c.343+137C>G	intron	N/A	ENSP00000221742.3	P48664-1
SLC1A6	ENST00000600144.5	TSL:1	c.343+137C>G	intron	N/A	ENSP00000471038.1	M0R063

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80908

AN:

151860

Hom.:

21819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.630

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.496

GnomAD4 exome

AF:

0.544

AC:

377340

AN:

694050

Hom.:

103897

AF XY:

0.545

AC XY:

194731

AN XY:

357072

show subpopulations

African (AFR)

AF:

0.508

AC:

8952

AN:

17614

American (AMR)

AF:

0.566

AC:

13217

AN:

23358

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

5954

AN:

15550

East Asian (EAS)

AF:

0.685

AC:

22895

AN:

33408

South Asian (SAS)

AF:

0.605

AC:

32355

AN:

53452

European-Finnish (FIN)

AF:

0.576

AC:

20187

AN:

35076

Middle Eastern (MID)

AF:

0.380

AC:

931

AN:

2452

European-Non Finnish (NFE)

AF:

0.532

AC:

254804

AN:

478896

Other (OTH)

AF:

0.527

AC:

18045

AN:

34244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

8387

16774

25162

33549

41936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4794

9588

14382

19176

23970

<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:

0.533

AC:

80958

AN:

151978

Hom.:

21830

Cov.:

AF XY:

0.539

AC XY:

40050

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.508

AC:

21056

AN:

41414

American (AMR)

AF:

0.556

AC:

8490

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1331

AN:

3468

East Asian (EAS)

AF:

0.684

AC:

3536

AN:

5170

South Asian (SAS)

AF:

0.630

AC:

3033

AN:

4816

European-Finnish (FIN)

AF:

0.583

AC:

6167

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.526

AC:

35752

AN:

67960

Other (OTH)

AF:

0.493

AC:

1041

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1916

3832

5749

7665

9581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.346

Hom.:

738

Bravo

AF:

0.528

Asia WGS

AF:

0.653

AC:

2271

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

(source)

DANN

Benign

0.59

PhyloP100

-0.10

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