Variant 6-110435930-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033125.4(SLC22A16):c.1343T>C(p.Met448Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC22A16
NM_033125.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.45

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A16	NM_033125.4 linkuse as main transcript	c.1343T>C	p.Met448Thr	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.1343T>C	p.Met448Thr	missense_variant	6/8	1	NM_033125.4	ENSP00000357915.3	Q86VW1-1
SLC22A16	ENST00000330550.8 linkuse as main transcript	c.1241T>C	p.Met414Thr	missense_variant	8/10	1		ENSP00000328583.4	Q86VW1-2
SLC22A16	ENST00000451557.5 linkuse as main transcript	c.1094T>C	p.Met365Thr	missense_variant	5/7	2		ENSP00000395642.1	X6RE50

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251196

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135754

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727186

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:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 28, 2024

The c.1343T>C (p.M448T) alteration is located in exon 6 (coding exon 6) of the SLC22A16 gene. This alteration results from a T to C substitution at nucleotide position 1343, causing the methionine (M) at amino acid position 448 to be replaced by a threonine (T). 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

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

.;T;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.63

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Uncertain

0.39

MutationAssessor

Uncertain

2.5

.;M;.

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.96, 0.95

.;D;P

Vest4

0.79, 0.75

MutPred

0.62

.;Gain of glycosylation at M448 (P = 0.0598);.;

MVP

0.40

MPC

0.077

ClinPred

0.98

GERP RS

4.5

Varity_R

0.76

gMVP

0.84

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