6-110442294-A-C

Position:

• chr6-110442294-A-C

Variant summary

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

The NM_033125.4(SLC22A16):​c.1133T>G​(p.Leu378Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A16 NM_033125.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38

Genes affected

SLC22A16 (HGNC:20302): (solute carrier family 22 member 16) This gene encodes a member of the organic zwitterion transporter protein family which transports carnitine. The encoded protein has also been shown to transport anticancer drugs like bleomycin (PMID: 20037140) successful treatment has been correlated with the level of activity of this transporter in tumor cells. [provided by RefSeq, Dec 2011]

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
SLC22A16	NM_033125.4	c.1133T>G	p.Leu378Trp	missense_variant	4/8	ENST00000368919.8	NP_149116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A16	ENST00000368919.8	c.1133T>G	p.Leu378Trp	missense_variant	4/8	1	NM_033125.4	ENSP00000357915.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Jun 17, 2024

The c.1133T>G (p.L378W) alteration is located in exon 4 (coding exon 4) of the SLC22A16 gene. This alteration results from a T to G substitution at nucleotide position 1133, causing the leucine (L) at amino acid position 378 to be replaced by a tryptophan (W). 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	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.29	.;T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.3	.;M;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.85	N;N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.12	T;D;T;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;.
Polyphen		1.0	.;D;D;.;.
Vest4		0.45, 0.44
MutPred		0.67		.;Gain of catalytic residue at L378 (P = 0.0349);.;.;.;
MVP		0.28
MPC		0.039
ClinPred		0.57	D
GERP RS		2.3
Varity_R		0.28
gMVP		0.81

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

LitVar

Other links and lift over

dbSNP: rs1774997854; hg19: chr6-110763497;