19-14972881-C-A

Variant names:

• chr19-14972881-C-A
• rs3746295
• NM_005071.3:c.30G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

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 -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	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 2 of 10	ENST00000594383.2	NP_005062.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79351 AN: 152042 Hom.: 20904 Cov.: 34

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

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.: 50 AF XY: 0.529 AC XY: 379227 AN XY: 716282

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

GnomAD4 genome AF: 0.522 AC: 79398 AN: 152160 Hom.: 20915 Cov.: 34 AF XY: 0.526 AC XY: 39133 AN XY: 74398

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

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	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.000062	T;T
MetaSVM	Benign	-0.90	T
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	T
GERP RS		4.4
PromoterAI		0.0046	Neutral
Mutation Taster		=75/25	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

Publications

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Other links and lift over

dbSNP: rs3746295; hg19: chr19-15083693; COSMIC: COSV55670989;