chr19-49293350-G-T

Position:

• chr19-49293350-G-T

Variant summary

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

The NM_014037.3(SLC6A16):​c.1651C>A​(p.Leu551Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign 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: 1.66

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A16	NM_014037.3	c.1651C>A	p.Leu551Ile	missense_variant	10/12	ENST00000335875.9	NP_054756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A16	ENST00000335875.9	c.1651C>A	p.Leu551Ile	missense_variant	10/12	5	NM_014037.3	ENSP00000338627.3
SLC6A16	ENST00000454748.7	c.1651C>A	p.Leu551Ile	missense_variant	10/11	1		ENSP00000404022.2
SLC6A16	ENST00000598828.1	c.286C>A	p.Leu96Ile	missense_variant	4/5	2		ENSP00000469885.1
SLC6A16	ENST00000598221.1	n.507C>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 22, 2024

The c.1651C>A (p.L551I) alteration is located in exon 10 (coding exon 9) of the SLC6A16 gene. This alteration results from a C to A substitution at nucleotide position 1651, causing the leucine (L) at amino acid position 551 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	0.085
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.027	D;D;.
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.20
MutPred		0.67		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;
MVP		0.85
MPC		0.63
ClinPred		0.49	T
GERP RS		0.79
Varity_R		0.18
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr19-49796607;