Variant chr2-11155572-G-A 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_152391.5(SLC66A3):c.26G>A(p.Cys9Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000198 in 1,513,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SLC66A3
NM_152391.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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:

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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, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC66A3	NM_152391.5 linkuse as main transcript	c.26G>A	p.Cys9Tyr	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.26G>A	p.Cys9Tyr	missense_variant	1/7	1	NM_152391.5	P1	Q8N755-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1361208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672672

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:

0.0000260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000910

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

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

Feb 13, 2024

The c.26G>A (p.C9Y) alteration is located in exon 1 (coding exon 1) of the PQLC3 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the cysteine (C) at amino acid position 9 to be replaced by a tyrosine (Y). 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

0.72

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Uncertain

0.57

.;.;D;D

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.8

.;L;L;.

MutationTaster

Benign

0.55

N;N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.99

.;.;D;.

Vest4

0.55, 0.51, 0.54

MutPred

0.61

.;Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);

MVP

0.99

MPC

0.93

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.68

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