3-11017195-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003042.4(SLC6A1):c.-17C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,609,842 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: SLC6A1 NM_003042.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.690

Genes affected

SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]

SLC6A1-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-11017195-C-T is Benign according to our data. Variant chr3-11017195-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00211 (322/152314) while in subpopulation NFE AF= 0.000661 (45/68032). AF 95% confidence interval is 0.000508. There are 7 homozygotes in gnomad4. There are 221 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.-17C>T		5_prime_UTR_variant	3/16	ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+1925G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-17C>T		5_prime_UTR_variant	3/16	1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+1925G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 322 AN: 152196 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00252 AC: 629 AN: 249748 Hom.: 11 AF XY: 0.00235 AC XY: 318 AN XY: 135288

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.000896

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00113 AC: 1649 AN: 1457528 Hom.: 16 Cov.: 30 AF XY: 0.00110 AC XY: 794 AN XY: 725060

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.000896

GnomAD4 genome AF: 0.00211 AC: 322 AN: 152314 Hom.: 7 Cov.: 32 AF XY: 0.00297 AC XY: 221 AN XY: 74462

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.000661

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.000283

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	SLC6A1: PP2, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs41362845; hg19: chr3-11058881; COSMIC: COSV55115832; COSMIC: COSV55115832;