19-49294019-C-T

Position:

• chr19-49294019-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014037.3(SLC6A16):​c.1426G>A​(p.Gly476Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC6A16 NM_014037.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A16	NM_014037.3	c.1426G>A	p.Gly476Ser	missense_variant	9/12	ENST00000335875.9	NP_054756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A16	ENST00000335875.9	c.1426G>A	p.Gly476Ser	missense_variant	9/12	5	NM_014037.3	ENSP00000338627.3
SLC6A16	ENST00000454748.7	c.1426G>A	p.Gly476Ser	missense_variant	9/11	1		ENSP00000404022.2
SLC6A16	ENST00000598828.1	c.61G>A	p.Gly21Ser	missense_variant	3/5	2		ENSP00000469885.1
SLC6A16	ENST00000598221.1	n.282G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1426G>A (p.G476S) alteration is located in exon 9 (coding exon 8) of the SLC6A16 gene. This alteration results from a G to A substitution at nucleotide position 1426, causing the glycine (G) at amino acid position 476 to be replaced by a serine (S). 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	Benign	0.16
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Benign	0.059
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.024	D
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.4	D;D;.
REVEL	Uncertain	0.34
Sift	Benign	0.15	T;T;.
Sift4G	Benign	0.12	T;T;.
Polyphen		0.99	D;.;.
Vest4		0.24
MutPred		0.86		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);.;
MVP		0.92
MPC		0.67
ClinPred		0.95	D
GERP RS		0.99
Varity_R		0.26
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49797276;