chr1-110167097-T-C

Variant names:

• chr1-110167097-T-C
• rs7527375
• NM_001010898.4:c.168T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001010898.4(SLC6A17):​c.168T>C​(p.Asp56Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,609,682 control chromosomes in the GnomAD database, including 213,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (18682 hom., cov: 24)
  • Exomes 𝑓: 0.51 (195309 hom.)
• Consequence: SLC6A17 NM_001010898.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.63
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-110167097-T-C is Benign according to our data. Variant chr1-110167097-T-C is described in ClinVar as Benign. ClinVar VariationId is 1333111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 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.168T>C	p.Asp56Asp	synonymous	Exon 2 of 12	NP_001010898.1	Q9H1V8
	SLC6A17-AS1	NR_183667.1		n.522A>G		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.168T>C	p.Asp56Asp	synonymous	Exon 2 of 12	ENSP00000330199.3	Q9H1V8
	SLC6A17-AS1	ENST00000430098.2	TSL:1	n.522A>G		non_coding_transcript_exon	Exon 2 of 3
	SLC6A17	ENST00000873463.1		c.168T>C	p.Asp56Asp	synonymous	Exon 2 of 12	ENSP00000543522.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 74104 AN: 149478 Hom.: 18666 Cov.: 24

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.451 AC: 111689 AN: 247750 AF XY: 0.454

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.510 AC: 744414 AN: 1460088 Hom.: 195309 Cov.: 73 AF XY: 0.507 AC XY: 367963 AN XY: 726180

African (AFR) AF: 0.503 AC: 16851 AN: 33472

American (AMR) AF: 0.276 AC: 12305 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12832 AN: 26110

East Asian (EAS) AF: 0.252 AC: 9974 AN: 39636

South Asian (SAS) AF: 0.360 AC: 30961 AN: 86086

European-Finnish (FIN) AF: 0.590 AC: 31331 AN: 53134

Middle Eastern (MID) AF: 0.436 AC: 2502 AN: 5736

European-Non Finnish (NFE) AF: 0.537 AC: 597124 AN: 1111076

Other (OTH) AF: 0.506 AC: 30534 AN: 60330

GnomAD4 genome AF: 0.496 AC: 74153 AN: 149594 Hom.: 18682 Cov.: 24 AF XY: 0.491 AC XY: 35838 AN XY: 72920

African (AFR) AF: 0.500 AC: 20291 AN: 40592

American (AMR) AF: 0.392 AC: 5903 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1674 AN: 3454

East Asian (EAS) AF: 0.223 AC: 1128 AN: 5056

South Asian (SAS) AF: 0.355 AC: 1636 AN: 4602

European-Finnish (FIN) AF: 0.589 AC: 6059 AN: 10290

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 35937 AN: 67292

Other (OTH) AF: 0.468 AC: 957 AN: 2046

Alfa AF: 0.502 Hom.: 7476

Bravo AF: 0.482

Asia WGS AF: 0.311 AC: 1084 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
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.086
DANN	Benign	0.62
PhyloP100		-5.6
Mutation Taster		=98/2	polymorphism (auto)

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: rs7527375; hg19: chr1-110709719; COSMIC: COSV58991969;