Variant 6-110435910-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033125.4(SLC22A16):c.1363G>A(p.Gly455Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLC22A16
NM_033125.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

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]

SLC22A16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18264979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A16	NM_033125.4 linkuse as main transcript	c.1363G>A	p.Gly455Arg	missense_variant	6/8	ENST00000368919.8	NP_149116.2	Q86VW1-1A0A0K0K1K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC22A16	ENST00000368919.8 linkuse as main transcript	c.1363G>A	p.Gly455Arg	missense_variant	6/8	1	NM_033125.4	ENSP00000357915.3	Q86VW1-1
SLC22A16	ENST00000330550.8 linkuse as main transcript	c.1261G>A	p.Gly421Arg	missense_variant	8/10	1		ENSP00000328583.4	Q86VW1-2
SLC22A16	ENST00000451557.5 linkuse as main transcript	c.1114G>A	p.Gly372Arg	missense_variant	5/7	2		ENSP00000395642.1	X6RE50

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000191

AC:

AN:

251174

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

185

AN:

1461732

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000800

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000138

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.1363G>A (p.G455R) alteration is located in exon 6 (coding exon 6) of the SLC22A16 gene. This alteration results from a G to A substitution at nucleotide position 1363, causing the glycine (G) at amino acid position 455 to be replaced by an arginine (R). 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

0.97

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.

Eigen

Benign

0.068

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Uncertain

2.9

.;M;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

N;N;N

REVEL

Uncertain

0.62

Sift

Uncertain

0.026

D;T;T

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.84, 0.78

MutPred

0.86

.;Gain of methylation at G455 (P = 0.0317);.;

MVP

0.33

MPC

0.12

ClinPred

0.15

GERP RS

2.9

Varity_R

0.25

gMVP

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over