NM_014228.5:c.690C>T

Variant names:

• chr5-150199333-C-T
• rs75182555
• NM_014228.5:c.690C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_014228.5(SLC6A7):​c.690C>T​(p.Leu230Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00893 in 1,614,098 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0092 (82 hom.)
• Consequence: SLC6A7 NM_014228.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 5-150199333-C-T is Benign according to our data. Variant chr5-150199333-C-T is described in ClinVar as Benign. ClinVar VariationId is 774636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.690C>T	p.Leu230Leu	synonymous	Exon 5 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.690C>T	p.Leu230Leu	synonymous	Exon 5 of 14	ENSP00000230671.2	Q99884
	SLC6A7	ENST00000524041.1	TSL:5	c.690C>T	p.Leu230Leu	synonymous	Exon 5 of 16	ENSP00000428200.1	E5RJL1

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 962 AN: 152222 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00550 AC: 1381 AN: 251208 AF XY: 0.00537

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00984

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00920 AC: 13444 AN: 1461760 Hom.: 82 Cov.: 32 AF XY: 0.00876 AC XY: 6372 AN XY: 727194

African (AFR) AF: 0.00102 AC: 34 AN: 33476

American (AMR) AF: 0.00289 AC: 129 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00410 AC: 107 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86236

European-Finnish (FIN) AF: 0.00234 AC: 125 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0112 AC: 12481 AN: 1111942

Other (OTH) AF: 0.00906 AC: 547 AN: 60392

GnomAD4 genome AF: 0.00631 AC: 962 AN: 152338 Hom.: 3 Cov.: 31 AF XY: 0.00561 AC XY: 418 AN XY: 74498

African (AFR) AF: 0.00226 AC: 94 AN: 41578

American (AMR) AF: 0.00418 AC: 64 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 745 AN: 68036

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00696 Hom.: 1

Bravo AF: 0.00587

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.0102

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs75182555; hg19: chr5-149578896;