19-14972881-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005071.3(SLC1A6):​c.30G>A​(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: SLC1A6 NM_005071.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 20 publications found

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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21270996).
• BP7: Synonymous conserved (PhyloP=0.286 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-0.097
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.45	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.38	T
PhyloP100		0.29
PROVEAN	Benign	0.090	N;.
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;.
Polyphen		0.079	B;.
Vest4		0.11
MutPred		0.088		Gain of phosphorylation at A15 (P = 0.0065);Gain of phosphorylation at A15 (P = 0.0065);
MVP		0.27
ClinPred		0.24	T
GERP RS		4.4
PromoterAI		-0.017	Neutral
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs3746295; hg19: chr19-15083693;