Variant chr2-11155679-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2

The NM_152391.5(SLC66A3):c.133G>C(p.Glu45Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000211 in 1,446,840 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

SLC66A3
NM_152391.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.52

Variant links:

Genes affected

SLC66A3 (HGNC:28503): (solute carrier family 66 member 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC66A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, M_CAP, MutationAssessor, PrimateAI, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.032732457).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC66A3	NM_152391.5 linkuse as main transcript	c.133G>C	p.Glu45Gln	missense_variant	1/7	ENST00000295083.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC66A3	ENST00000295083.8 linkuse as main transcript	c.133G>C	p.Glu45Gln	missense_variant	1/7	1	NM_152391.5	P1	Q8N755-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000290

AC:

AN:

96482

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

55866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000398

Gnomad OTH exome

AF:

0.000518

GnomAD4 exome

AF:

0.000204

AC:

264

AN:

1294674

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

124

AN XY:

635766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00860

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000521

Gnomad4 OTH exome

AF:

0.000699

GnomAD4 genome

AF:

0.000269

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000306

ExAC

AF:

0.000229

AC:

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

Dec 06, 2021

The c.133G>C (p.E45Q) alteration is located in exon 1 (coding exon 1) of the PQLC3 gene. This alteration results from a G to C substitution at nucleotide position 133, causing the glutamic acid (E) at amino acid position 45 to be replaced by a glutamine (Q). 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

0.73

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

.;.;D;D

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.1

.;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.73, 0.70, 0.75

MutPred

0.71

.;Gain of glycosylation at P40 (P = 0.1793);Gain of glycosylation at P40 (P = 0.1793);Gain of glycosylation at P40 (P = 0.1793);

MVP

0.95

MPC

0.72

ClinPred

0.42

GERP RS

4.6

Varity_R

0.73

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