2-11164206-T-G

Position:

• chr2-11164206-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152391.5(SLC66A3):​c.299T>G​(p.Leu100Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC66A3 NM_152391.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38006443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC66A3	NM_152391.5	c.299T>G	p.Leu100Trp	missense_variant, splice_region_variant	4/7	ENST00000295083.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC66A3	ENST00000295083.8	c.299T>G	p.Leu100Trp	missense_variant, splice_region_variant	4/7	1	NM_152391.5	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 30

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

Mar 30, 2024

The c.299T>G (p.L100W) alteration is located in exon 4 (coding exon 4) of the PQLC3 gene. This alteration results from a T to G substitution at nucleotide position 299, causing the leucine (L) at amino acid position 100 to be replaced by a tryptophan (W). 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	0.19
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.22	.;.;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.90	.;L;L;.
MutationTaster	Benign	0.90	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.024	D;D;D;D
Sift4G	Benign	0.073	T;T;T;D
Polyphen		0.69	.;.;P;.
Vest4		0.49, 0.50, 0.52
MutPred		0.46		.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.91
MPC		0.46
ClinPred		0.39	T
GERP RS		2.0
Varity_R		0.050
gMVP		0.84

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: chr2-11304332;