Variant 2-11164259-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 NM_152391.5(SLC66A3):c.352A>G(p.Met118Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000387 in 1,550,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

SLC66A3
NM_152391.5 missense, splice_region

Scores

Splicing: ADA: 0.005081

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

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 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
SLC66A3	NM_152391.5 link	c.352A>G	p.Met118Val	missense_variant, splice_region_variant	4/7	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.352A>G	p.Met118Val	missense_variant, splice_region_variant	4/7	1	NM_152391.5	ENSP00000295083.3		Q8N755-1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399254

Hom.:

Cov.:

AF XY:

0.00000431

AC XY:

AN XY:

695346

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:

0.0000262

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73748

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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 09, 2024

The c.352A>G (p.M118V) alteration is located in exon 4 (coding exon 4) of the PQLC3 gene. This alteration results from a A to G substitution at nucleotide position 352, causing the methionine (M) at amino acid position 118 to be replaced by a valine (V). 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

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.047

.;.;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.7

.;L;L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.62

Sift

Benign

0.31

T;T;T;D

Sift4G

Uncertain

0.042

D;T;T;D

Polyphen

0.58

.;.;P;.

Vest4

0.74, 0.74, 0.69

MutPred

0.56

.;Gain of MoRF binding (P = 0.2924);Gain of MoRF binding (P = 0.2924);Gain of MoRF binding (P = 0.2924);

MVP

0.87

MPC

0.18

ClinPred

0.65

GERP RS

5.7

Varity_R

0.23

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0051

dbscSNV1_RF

Benign

0.066

SpliceAI score (max)

0.020

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