Variant 3-38307345-T-C 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_001320033.2(SLC22A14):c.608T>C(p.Leu203Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC22A14
NM_001320033.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

SLC22A14 (HGNC:8495): (solute carrier family 22 member 14) This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 3. The encoded protein is a transmembrane protein which is thought to transport small molecules and since this protein is conserved among several species, it is suggested to have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SLC22A14 links:

SLC22A14 (HGNC:):

SLC22A14 links:

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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=0.21607718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A14	NM_001320033.2 linkuse as main transcript	c.608T>C	p.Leu203Pro	missense_variant	3/11	ENST00000448498.6	NP_001306962.1	Q9Y267

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC22A14	ENST00000448498.6 linkuse as main transcript	c.608T>C	p.Leu203Pro	missense_variant	3/11	1	NM_001320033.2	ENSP00000396283.1	Q9Y267
SLC22A14	ENST00000273173.4 linkuse as main transcript	c.608T>C	p.Leu203Pro	missense_variant	2/10	1		ENSP00000273173.4	Q9Y267
SLC22A14	ENST00000466887.5 linkuse as main transcript	c.212T>C	p.Leu71Pro	missense_variant	3/4	4		ENSP00000442528.1	F5H7H1
SLC22A14	ENST00000496724.1 linkuse as main transcript	n.1461T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726808

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:

0.00

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

Aug 10, 2021

The c.608T>C (p.L203P) alteration is located in exon 2 (coding exon 2) of the SLC22A14 gene. This alteration results from a T to C substitution at nucleotide position 608, causing the leucine (L) at amino acid position 203 to be replaced by a proline (P). 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

Benign

0.13

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.016

.;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.43

T;.;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

.;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

2.8

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0020

.;B;B

Vest4

0.17, 0.16

MutPred

0.64

.;Loss of stability (P = 9e-04);Loss of stability (P = 9e-04);

MVP

0.25

MPC

0.63

ClinPred

0.30

GERP RS

3.6

Varity_R

0.094

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over