Variant 1-19326280-A-G 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.418A>G(p.Met140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC66A1
NM_001040125.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

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:

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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=0.07314277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC66A1	NM_001040125.2 linkuse as main transcript	c.418A>G	p.Met140Val	missense_variant	5/8	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.418A>G	p.Met140Val	missense_variant	5/8	2	NM_001040125.2	ENSP00000364295.3		Q6ZP29-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

245918

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454406

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723806

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jun 09, 2022

The c.418A>G (p.M140V) alteration is located in exon 5 (coding exon 4) of the PQLC2 gene. This alteration results from a A to G substitution at nucleotide position 418, causing the methionine (M) at amino acid position 140 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

0.064

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0010

DANN

Benign

0.34

DEOGEN2

Benign

0.0017

T;T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.47

.;T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.073

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

N;N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.31

N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.049

MutPred

0.46

Loss of stability (P = 0.5131);Loss of stability (P = 0.5131);.;.;

MVP

0.15

MPC

0.34

ClinPred

0.047

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.28

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