Genetic Variant NM_005071.3:c.30G>T (chr19-14972881-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005071.3(SLC1A6):c.30G>T(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,595,290 control chromosomes in the GnomAD database, including 224,351 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 0.52 ( 20915 hom., cov: 34)

Exomes 𝑓: 0.53 ( 203436 hom. )

Consequence

SLC1A6
NM_005071.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.286

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.1753024E-5).

BP7

Synonymous conserved (PhyloP=0.286 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A6	NM_005071.3 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 2 of 10	ENST00000594383.2	NP_005062.1	P48664-1B7Z7Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A6	ENST00000594383.2 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 2 of 10	2	NM_005071.3	ENSP00000472133.2		P48664-1M0R1V3

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79351

AN:

152042

Hom.:

20904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.486

GnomAD2 exomes

AF:

0.532

AC:

111072

AN:

208772

AF XY:

0.533

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.642

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.529

AC:

763710

AN:

1443130

Hom.:

203436

Cov.:

AF XY:

0.529

AC XY:

379227

AN XY:

716282

show subpopulations

African (AFR)

AF:

0.497

AC:

16516

AN:

33218

American (AMR)

AF:

0.486

AC:

20144

AN:

41452

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9608

AN:

25660

East Asian (EAS)

AF:

0.656

AC:

25595

AN:

39044

South Asian (SAS)

AF:

0.548

AC:

46066

AN:

84076

European-Finnish (FIN)

AF:

0.579

AC:

29689

AN:

51312

Middle Eastern (MID)

AF:

0.365

AC:

1960

AN:

5376

European-Non Finnish (NFE)

AF:

0.529

AC:

583448

AN:

1103336

Other (OTH)

AF:

0.514

AC:

30684

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18633

37265

55898

74530

93163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.522

AC:

79398

AN:

152160

Hom.:

20915

Cov.:

AF XY:

0.526

AC XY:

39133

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.502

AC:

20851

AN:

41516

American (AMR)

AF:

0.503

AC:

7698

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1306

AN:

3466

East Asian (EAS)

AF:

0.647

AC:

3342

AN:

5168

South Asian (SAS)

AF:

0.569

AC:

2745

AN:

4826

European-Finnish (FIN)

AF:

0.582

AC:

6167

AN:

10602

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.526

AC:

35724

AN:

67964

Other (OTH)

AF:

0.482

AC:

1018

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2017

4035

6052

8070

10087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.522

Hom.:

40386

Bravo

AF:

0.514

TwinsUK

AF:

0.528

AC:

1956

ALSPAC

AF:

0.517

AC:

1993

ESP6500AA

AF:

0.521

AC:

2182

ESP6500EA

AF:

0.533

AC:

4397

ExAC

AF:

0.506

AC:

60307

Asia WGS

AF:

0.596

AC:

2072

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.000062

T;T

MetaSVM

Benign

-0.90

PhyloP100

0.29

PROVEAN

Benign

-0.52

N;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.

Polyphen

0.018

B;.

Vest4

0.074

ClinPred

0.039

GERP RS

4.4

PromoterAI

0.0046

Neutral

(source)

Mutation Taster

=75/25

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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NM_005071.3:c.30G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over