chr19-49293841-G-A

Variant names:

• chr19-49293841-G-A
• rs1600606681
• NM_014037.3:c.1604C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014037.3(SLC6A16):​c.1604C>T​(p.Thr535Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T535R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A16 NM_014037.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2690944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014037.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A16	NM_014037.3	MANE Select	c.1604C>T	p.Thr535Ile	missense	Exon 9 of 12	NP_054756.2	Q9GZN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A16	ENST00000335875.9	TSL:5 MANE Select	c.1604C>T	p.Thr535Ile	missense	Exon 9 of 12	ENSP00000338627.3	Q9GZN6-1
	SLC6A16	ENST00000454748.7	TSL:1	c.1604C>T	p.Thr535Ile	missense	Exon 9 of 11	ENSP00000404022.2	Q9GZN6-2
	SLC6A16	ENST00000598828.1	TSL:2	c.239C>T	p.Thr80Ile	missense	Exon 3 of 5	ENSP00000469885.1	M0QYK3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.8
DANN	Benign	0.92
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.58
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.14
Sift	Benign	0.066	T
Sift4G	Benign	0.085	T
Polyphen		0.37	B
Vest4		0.20
MutPred		0.70		Gain of MoRF binding (P = 0.0904)
MVP		0.69
MPC		0.38
ClinPred		0.45	T
GERP RS		-0.37
Varity_R		0.14
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1600606681; hg19: chr19-49797098;