Variant 19-49293889-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014037.3(SLC6A16):c.1556G>T(p.Gly519Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC6A16
NM_014037.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

SLC6A16 (HGNC:13622): (solute carrier family 6 member 16) SLC6A16 shows structural characteristics of an Na(+)- and Cl(-)-dependent neurotransmitter transporter, including 12 transmembrane (TM) domains, intracellular N and C termini, and large extracellular loops containing multiple N-glycosylation sites.[supplied by OMIM, Mar 2008]

SLC6A16 links:

SLC6A16 (HGNC:):

SLC6A16 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A16	NM_014037.3 linkuse as main transcript	c.1556G>T	p.Gly519Val	missense_variant	9/12	ENST00000335875.9	NP_054756.2	Q9GZN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC6A16	ENST00000335875.9 linkuse as main transcript	c.1556G>T	p.Gly519Val	missense_variant	9/12	5	NM_014037.3	ENSP00000338627.3	Q9GZN6-1
SLC6A16	ENST00000454748.7 linkuse as main transcript	c.1556G>T	p.Gly519Val	missense_variant	9/11	1		ENSP00000404022.2	Q9GZN6-2
SLC6A16	ENST00000598828.1 linkuse as main transcript	c.191G>T	p.Gly64Val	missense_variant	3/5	2		ENSP00000469885.1	M0QYK3
SLC6A16	ENST00000598221.1 linkuse as main transcript	n.412G>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.1556G>T (p.G519V) alteration is located in exon 9 (coding exon 8) of the SLC6A16 gene. This alteration results from a G to T substitution at nucleotide position 1556, causing the glycine (G) at amino acid position 519 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Benign

-0.29

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-8.3

D;D;.

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0060

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.70

MutPred

0.87

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;

MVP

0.86

MPC

0.79

ClinPred

0.94

GERP RS

0.98

Varity_R

0.63

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over