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

Variant summary

Our verdict is Benign. Variant got -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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.532

AC:

111072

AN:

208772

Hom.:

29614

AF XY:

0.533

AC XY:

61115

AN XY:

114638

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 SAS exome

AF:

0.555

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

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.656

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.514

GnomAD4 genome

AF:

0.522

AC:

79398

AN:

152160

Hom.:

20915

Cov.:

AF XY:

0.526

AC XY:

39133

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.514

Hom.:

14674

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over