chr5-150197110-G-T

Variant names:

• chr5-150197110-G-T
• NM_014228.5:c.418G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014228.5(SLC6A7):​c.418G>T​(p.Val140Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A7 NM_014228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

Genes affected

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A7	NM_014228.5	c.418G>T	p.Val140Leu	missense_variant	Exon 4 of 14	ENST00000230671.7	NP_055043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A7	ENST00000230671.7	c.418G>T	p.Val140Leu	missense_variant	Exon 4 of 14	1	NM_014228.5	ENSP00000230671.2
SLC6A7	ENST00000524041.1	c.418G>T	p.Val140Leu	missense_variant	Exon 4 of 16	5		ENSP00000428200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	0.0027	D
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.54	P;.
Vest4		0.54
MutPred		0.71		Loss of catalytic residue at V140 (P = 0.126);Loss of catalytic residue at V140 (P = 0.126);
MVP		0.79
MPC		0.72
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.45
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149576673;