Variant 1-19325571-G-A 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_001040125.2(SLC66A1):c.371G>A(p.Arg124His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,392,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC66A1
NM_001040125.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

SLC66A1 (HGNC:26001): (solute carrier family 66 member 1) Enables L-arginine transmembrane transporter activity and L-lysine transmembrane transporter activity. Involved in L-arginine transmembrane transport; amino acid homeostasis; and lysine transport. Located in lysosomal membrane. Is integral component of organelle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC66A1 links:

SLC66A1 (HGNC:):

SLC66A1 links:

Genome browser will be placed here

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=0.17459527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC66A1	NM_001040125.2 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	4/8	ENST00000375153.8	NP_001035214.1	Q6ZP29-1A0A024RAE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC66A1	ENST00000375153.8 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	4/8	2	NM_001040125.2	ENSP00000364295.3		Q6ZP29-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147488

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250950

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1392554

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

693448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000699

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000211

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

147488

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72088

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jun 06, 2023

The c.371G>A (p.R124H) alteration is located in exon 4 (coding exon 3) of the PQLC2 gene. This alteration results from a G to A substitution at nucleotide position 371, causing the arginine (R) at amino acid position 124 to be replaced by a histidine (H). 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

0.086

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

T;T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Uncertain

-0.053

MutationAssessor

Uncertain

2.6

M;M;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.063

T;T;D;D

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

0.054

B;B;.;.

Vest4

0.27

MutPred

0.43

Loss of solvent accessibility (P = 0.0128);Loss of solvent accessibility (P = 0.0128);.;.;

MVP

0.71

MPC

0.43

ClinPred

0.14

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.048

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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