5-150197110-G-T

Variant names:

• chr5-150197110-G-T
• rs370151097
• NM_014228.5:c.418G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V140M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A7 NM_014228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	NM_014228.5	MANE Select	c.418G>T	p.Val140Leu	missense	Exon 4 of 14	NP_055043.2	Q99884

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	ENST00000230671.7	TSL:1 MANE Select	c.418G>T	p.Val140Leu	missense	Exon 4 of 14	ENSP00000230671.2	Q99884
	SLC6A7	ENST00000524041.1	TSL:5	c.418G>T	p.Val140Leu	missense	Exon 4 of 16	ENSP00000428200.1	E5RJL1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.0027	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.013	D
Polyphen		0.54	P
Vest4		0.54
MutPred		0.71		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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs370151097; hg19: chr5-149576673;