18-79919242-T-C

Variant names:

• chr18-79919242-T-C
• NM_025078.5:c.550A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025078.5(SLC66A2):​c.550A>G​(p.Met184Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC66A2 NM_025078.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

Genes affected

SLC66A2 (HGNC:26188): (solute carrier family 66 member 2) Predicted to be involved in phospholipid translocation and retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be integral component of membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC66A2	NM_025078.5	c.550A>G	p.Met184Val	missense_variant	Exon 5 of 6	ENST00000397778.7	NP_079354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC66A2	ENST00000397778.7	c.550A>G	p.Met184Val	missense_variant	Exon 5 of 6	1	NM_025078.5	ENSP00000380880.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550A>G (p.M184V) alteration is located in exon 5 (coding exon 4) of the PQLC1 gene. This alteration results from a A to G substitution at nucleotide position 550, causing the methionine (M) at amino acid position 184 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	0.21
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	.;D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.098	.;B
Vest4		0.73
MutPred		0.43		.;Loss of helix (P = 0.2022);
MVP		0.60
MPC		0.23
ClinPred		0.83	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.68

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: chr18-77679242;