19-14972881-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005071.3(SLC1A6):​c.30G>C​(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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24014452).
• 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>C	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>C	p.Leu10Leu	synonymous_variant	Exon 2 of 10	2	NM_005071.3	ENSP00000472133.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1443678 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 716582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-0.070
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.41	T;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.33	T
PROVEAN	Benign	-0.86	N;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;.
Polyphen		0.15	B;.
Vest4		0.16
MutPred		0.069		Gain of catalytic residue at P14 (P = 0.0119);Gain of catalytic residue at P14 (P = 0.0119);
MVP		0.30
ClinPred		0.24	T
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

Other links and lift over

dbSNP: rs3746295; hg19: chr19-15083693;