1-110167098-G-A

Variant names:

• chr1-110167098-G-A
• rs12737742
• NM_001010898.4:c.169G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010898.4(SLC6A17):​c.169G>A​(p.Ala57Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,610,442 control chromosomes in the GnomAD database, including 153,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10392 hom., cov: 25)
  • Exomes 𝑓: 0.43 (143349 hom.)
• Consequence: SLC6A17 NM_001010898.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.681
• Publications: 21 publications found

Genes affected

SLC6A17 (HGNC:31399): (solute carrier family 6 member 17) The protein encoded by this gene is a member of the SLC6 family of transporters, which are responsible for the presynaptic uptake of most neurotransmitters. The encoded vesicular transporter is selective for proline, glycine, leucine and alanine. In mouse, the strongest expression of this gene was in cortical and hippocampal tissues where expression increased during embryonic brain development and peaked postnatally. Defects in this gene cause a form of autosomal recessive intellectual disability. [provided by RefSeq, Jul 2017]

SLC6A17-AS1 (HGNC:41279): (SLC6A17 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.933941E-5).
• BP6: Variant 1-110167098-G-A is Benign according to our data. Variant chr1-110167098-G-A is described in ClinVar as Benign. ClinVar VariationId is 1333112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010898.4. 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
	SLC6A17	NM_001010898.4	MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 2 of 12	NP_001010898.1	Q9H1V8
	SLC6A17-AS1	NR_183667.1		n.521C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A17	ENST00000331565.5	TSL:2 MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 2 of 12	ENSP00000330199.3	Q9H1V8
	SLC6A17-AS1	ENST00000430098.2	TSL:1	n.521C>T		non_coding_transcript_exon	Exon 2 of 3
	SLC6A17	ENST00000873463.1		c.169G>A	p.Ala57Thr	missense	Exon 2 of 12	ENSP00000543522.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50402 AN: 150100 Hom.: 10397 Cov.: 25

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.372 AC: 92386 AN: 248036 AF XY: 0.383

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.433 AC: 632925 AN: 1460224 Hom.: 143349 Cov.: 72 AF XY: 0.433 AC XY: 314689 AN XY: 726238

African (AFR) AF: 0.0813 AC: 2722 AN: 33468

American (AMR) AF: 0.220 AC: 9799 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 11970 AN: 26106

East Asian (EAS) AF: 0.251 AC: 9960 AN: 39648

South Asian (SAS) AF: 0.341 AC: 29382 AN: 86100

European-Finnish (FIN) AF: 0.534 AC: 28369 AN: 53152

Middle Eastern (MID) AF: 0.379 AC: 2176 AN: 5736

European-Non Finnish (NFE) AF: 0.462 AC: 513282 AN: 1111150

Other (OTH) AF: 0.419 AC: 25265 AN: 60340

GnomAD4 genome AF: 0.335 AC: 50386 AN: 150218 Hom.: 10392 Cov.: 25 AF XY: 0.338 AC XY: 24755 AN XY: 73240

African (AFR) AF: 0.0964 AC: 3957 AN: 41040

American (AMR) AF: 0.298 AC: 4498 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1566 AN: 3454

East Asian (EAS) AF: 0.222 AC: 1125 AN: 5074

South Asian (SAS) AF: 0.335 AC: 1541 AN: 4598

European-Finnish (FIN) AF: 0.535 AC: 5534 AN: 10336

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 30974 AN: 67368

Other (OTH) AF: 0.338 AC: 693 AN: 2050

Alfa AF: 0.416 Hom.: 30244

Bravo AF: 0.308

TwinsUK AF: 0.452 AC: 1675

ALSPAC AF: 0.455 AC: 1754

ESP6500AA AF: 0.108 AC: 477

ESP6500EA AF: 0.445 AC: 3831

ExAC AF: 0.371 AC: 45076

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.000069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.68
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.083
Sift	Benign	0.55	T
Sift4G	Benign	0.44	T
Polyphen		0.049	B
Vest4		0.039
MPC		0.54
ClinPred		0.0035	T
GERP RS		2.6
Varity_R		0.027
gMVP		0.14
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12737742; hg19: chr1-110709720; COSMIC: COSV58993671;