Variant 2-11155672-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152391.5(SLC66A3):c.126A>C(p.Leu42Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,454,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

SLC66A3
NM_152391.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.997

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2732873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC66A3	NM_152391.5 link	c.126A>C	p.Leu42Phe	missense_variant	1/7	ENST00000295083.8	NP_689604.1	Q8N755-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC66A3	ENST00000295083.8 link	c.126A>C	p.Leu42Phe	missense_variant	1/7	1	NM_152391.5	ENSP00000295083.3		Q8N755-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000951

AC:

AN:

105188

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

61192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000723

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000921

AC:

AN:

1302230

Hom.:

Cov.:

AF XY:

0.00000937

AC XY:

AN XY:

640408

show subpopulations

Gnomad4 AFR exome

AF:

0.000336

Gnomad4 AMR exome

AF:

0.0000412

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:

0.0000376

GnomAD4 genome

AF:

0.000309

AC:

AN:

151974

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.000918

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000561

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000876

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 03, 2024

The c.126A>C (p.L42F) alteration is located in exon 1 (coding exon 1) of the PQLC3 gene. This alteration results from a A to C substitution at nucleotide position 126, causing the leucine (L) at amino acid position 42 to be replaced by a phenylalanine (F). 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

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.38

.;.;T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

.;L;L;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.016

D;D;D;D

Sift4G

Benign

0.070

T;T;T;D

Polyphen

1.0

.;.;D;.

Vest4

0.49, 0.44, 0.49

MutPred

0.66

.;Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);

MVP

0.83

MPC

0.74

ClinPred

0.89

GERP RS

-7.8

Varity_R

0.46

gMVP

0.64

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