1-110172197-A-G

Position:

• chr1-110172197-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_001010898.4(SLC6A17):​c.424A>G​(p.Ile142Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,597,072 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (3 hom.)
• Consequence: SLC6A17 NM_001010898.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.32

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

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC6A17. . Gene score misZ 2.3852 (greater than the threshold 3.09). Trascript score misZ 3.6036 (greater than threshold 3.09). GenCC has associacion of gene with progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, schizophrenia.
• BP4: Computational evidence support a benign effect (MetaRNN=0.024453431).
• BP6: Variant 1-110172197-A-G is Benign according to our data. Variant chr1-110172197-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 774584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A17	NM_001010898.4	c.424A>G	p.Ile142Val	missense_variant	3/12	ENST00000331565.5	NP_001010898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A17	ENST00000331565.5	c.424A>G	p.Ile142Val	missense_variant	3/12	2	NM_001010898.4	ENSP00000330199	P1
SLC6A17-AS1	ENST00000443008.1	n.293T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000747 AC: 163 AN: 218184 Hom.: 1 AF XY: 0.000748 AC XY: 88 AN XY: 117624

Gnomad AFR exome AF: 0.0000741

Gnomad AMR exome AF: 0.000353

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00233

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000729

GnomAD4 exome AF: 0.000816 AC: 1179 AN: 1444828 Hom.: 3 Cov.: 30 AF XY: 0.000771 AC XY: 553 AN XY: 717268

Gnomad4 AFR exome AF: 0.000151

Gnomad4 AMR exome AF: 0.000308

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00255

Gnomad4 NFE exome AF: 0.000884

Gnomad4 OTH exome AF: 0.000820

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.000833 AC XY: 62 AN XY: 74438

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000822 Hom.: 0

Bravo AF: 0.000567

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.000875 AC: 106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.38
Sift	Benign	0.15	T
Sift4G	Benign	0.55	T
Polyphen		1.0	D
Vest4		0.54
MVP		0.67
MPC		1.4
ClinPred		0.12	T
GERP RS		5.2
Varity_R		0.18
gMVP		0.36

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: rs148377467; hg19: chr1-110714819;