Variant 6-110431212-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000368919.8(SLC22A16):c.1480T>C(p.Phe494Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC22A16
ENST00000368919.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.782

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:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1480T>C	p.Phe494Leu	missense_variant	7/8	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.1480T>C	p.Phe494Leu	missense_variant	7/8	1	NM_033125.4	ENSP00000357915	P2	Q86VW1-1
SLC22A16	ENST00000330550.8 linkuse as main transcript	c.1378T>C	p.Phe460Leu	missense_variant	9/10	1		ENSP00000328583	A2	Q86VW1-2
SLC22A16	ENST00000451557.5 linkuse as main transcript	c.1231T>C	p.Phe411Leu	missense_variant	6/7	2		ENSP00000395642

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727054

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Oct 20, 2023

The c.1480T>C (p.F494L) alteration is located in exon 7 (coding exon 7) of the SLC22A16 gene. This alteration results from a T to C substitution at nucleotide position 1480, causing the phenylalanine (F) at amino acid position 494 to be replaced by a leucine (L). 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

0.74

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.3

DANN

Benign

0.77

DEOGEN2

Benign

0.27

.;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.16

Sift

Benign

0.083

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.47, 0.099

.;P;B

Vest4

0.29, 0.31

MutPred

0.72

.;Loss of glycosylation at S495 (P = 0.1794);.;

MVP

0.16

MPC

0.018

ClinPred

0.66

GERP RS

0.21

Varity_R

0.18

gMVP

0.69

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