Variant 6-110425056-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000368919.8(SLC22A16):c.1551T>G(p.Ser517Arg) 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 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC22A16
ENST00000368919.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A16	NM_033125.4 linkuse as main transcript	c.1551T>G	p.Ser517Arg	missense_variant	8/8	ENST00000368919.8	NP_149116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A16	ENST00000368919.8 linkuse as main transcript	c.1551T>G	p.Ser517Arg	missense_variant	8/8	1	NM_033125.4	ENSP00000357915	P2	Q86VW1-1
SLC22A16	ENST00000330550.8 linkuse as main transcript	c.1449T>G	p.Ser483Arg	missense_variant	10/10	1		ENSP00000328583	A2	Q86VW1-2
SLC22A16	ENST00000451557.5 linkuse as main transcript	c.*300T>G		3_prime_UTR_variant	7/7	2		ENSP00000395642
SLC22A16	ENST00000460159.1 linkuse as main transcript	n.97T>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251232

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 02, 2023

The c.1551T>G (p.S517R) alteration is located in exon 8 (coding exon 8) of the SLC22A16 gene. This alteration results from a T to G substitution at nucleotide position 1551, causing the serine (S) at amino acid position 517 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

0.99

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

D;.

Eigen

Benign

0.097

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

N;N

REVEL

Uncertain

0.48

Sift

Benign

0.055

T;D

Sift4G

Benign

0.069

T;T

Polyphen

0.99

D;D

Vest4

0.71

MutPred

0.91

Gain of methylation at S517 (P = 0.0267);.;

MVP

0.28

MPC

0.11

ClinPred

0.87

GERP RS

1.4

Varity_R

0.84

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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