5-150197230-C-T

Variant names:

• chr5-150197230-C-T
• rs764953105
• NM_014228.5:c.538C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014228.5(SLC6A7):​c.538C>T​(p.Pro180Ser) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. 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. P180A) 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: 0.306
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10885438).

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.538C>T	p.Pro180Ser	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.538C>T	p.Pro180Ser	missense	Exon 4 of 14	ENSP00000230671.2	Q99884
	SLC6A7	ENST00000524041.1	TSL:5	c.538C>T	p.Pro180Ser	missense	Exon 4 of 16	ENSP00000428200.1	E5RJL1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248854 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.32	N
PhyloP100		0.31
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.057
Sift	Benign	0.35	T
Sift4G	Benign	0.74	T
Polyphen		0.0090	B
Vest4		0.32
MutPred		0.38		Gain of sheet (P = 0.0477)
MVP		0.74
MPC		0.22
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.048
gMVP		0.61
Mutation Taster		=88/12	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: rs764953105; hg19: chr5-149576793;