1-19326332-C-T

Position:

• chr1-19326332-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040125.2(SLC66A1):​c.470C>T​(p.Ala157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000021 (0 hom.)
• Consequence: SLC66A1 NM_001040125.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0270

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0563412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC66A1	NM_001040125.2	c.470C>T	p.Ala157Val	missense_variant	5/8	ENST00000375153.8	NP_001035214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC66A1	ENST00000375153.8	c.470C>T	p.Ala157Val	missense_variant	5/8	2	NM_001040125.2	ENSP00000364295.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454442 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 723868

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Dec 19, 2022

The c.470C>T (p.A157V) alteration is located in exon 5 (coding exon 4) of the PQLC2 gene. This alteration results from a C to T substitution at nucleotide position 470, causing the alanine (A) at amino acid position 157 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	0.073
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0013	T;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.11	N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.13
MutPred		0.34		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;.;
MVP		0.15
MPC		0.33
ClinPred		0.039	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-19652826;