5-150197076-G-C

Position:

• chr5-150197076-G-C

Variant summary

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

The NM_014228.5(SLC6A7):​c.384G>C​(p.Leu128Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict 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: 33)
• Consequence: SLC6A7 NM_014228.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.580

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/exons	MANE	Protein	UniProt
SLC6A7	NM_014228.5	c.384G>C	p.Leu128Phe	missense_variant	4/14	ENST00000230671.7	NP_055043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A7	ENST00000230671.7	c.384G>C	p.Leu128Phe	missense_variant	4/14	1	NM_014228.5	ENSP00000230671.2
SLC6A7	ENST00000524041.1	c.384G>C	p.Leu128Phe	missense_variant	4/16	5		ENSP00000428200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.384G>C (p.L128F) alteration is located in exon 4 (coding exon 4) of the SLC6A7 gene. This alteration results from a G to C substitution at nucleotide position 384, causing the leucine (L) at amino acid position 128 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.51	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.75	P;.
Vest4		0.62
MutPred		0.52		Loss of catalytic residue at L128 (P = 0.1075);Loss of catalytic residue at L128 (P = 0.1075);
MVP		0.79
MPC		0.77
ClinPred		0.77	D
GERP RS		1.3
Varity_R		0.22
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149576639;