1-19326591-C-G

Position:

• chr1-19326591-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001040125.2(SLC66A1):​c.586C>G​(p.Leu196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC66A1 NM_001040125.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC66A1	NM_001040125.2	c.586C>G	p.Leu196Val	missense_variant	6/8	ENST00000375153.8	NP_001035214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC66A1	ENST00000375153.8	c.586C>G	p.Leu196Val	missense_variant	6/8	2	NM_001040125.2	ENSP00000364295.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.586C>G (p.L196V) alteration is located in exon 6 (coding exon 5) of the PQLC2 gene. This alteration results from a C to G substitution at nucleotide position 586, causing the leucine (L) at amino acid position 196 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	0.29
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;.;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.2	M;M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Pathogenic	0.71
Sift	Benign	0.071	T;T;D;D
Sift4G	Uncertain	0.020	D;D;D;D
Polyphen		0.88	P;P;.;.
Vest4		0.72
MutPred		0.66		Gain of MoRF binding (P = 0.1175);Gain of MoRF binding (P = 0.1175);.;.;
MVP		0.75
MPC		0.92
ClinPred		0.86	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-19653085;