19-49290149-G-T

Variant names:

• chr19-49290149-G-T
• NM_014037.3:c.2185C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014037.3(SLC6A16):​c.2185C>A​(p.Pro729Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC6A16 NM_014037.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.464

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07592201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A16	NM_014037.3	c.2185C>A	p.Pro729Thr	missense_variant	Exon 12 of 12	ENST00000335875.9	NP_054756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A16	ENST00000335875.9	c.2185C>A	p.Pro729Thr	missense_variant	Exon 12 of 12	5	NM_014037.3	ENSP00000338627.3
SLC6A16	ENST00000454748	c.*417C>A		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000404022.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2185C>A (p.P729T) alteration is located in exon 12 (coding exon 11) of the SLC6A16 gene. This alteration results from a C to A substitution at nucleotide position 2185, causing the proline (P) at amino acid position 729 to be replaced by a threonine (T). 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	0.064
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.87
DANN	Benign	0.87
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.094
Sift	Uncertain	0.024	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.66	P
Vest4		0.10
MutPred		0.19		Loss of loop (P = 0.0603);
MVP		0.61
MPC		0.26
ClinPred		0.077	T
GERP RS		1.5
Varity_R		0.031
gMVP		0.073

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: chr19-49793406;