10-80432092-A-G

Variant names:

• chr10-80432092-A-G
• NM_032333.5:c.683A>G

Variant summary

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

The NM_032333.5(PRXL2A):​c.683A>G​(p.Lys228Arg) 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 benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K228E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRXL2A NM_032333.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.959

Genes affected

PRXL2A (HGNC:28651): (peroxiredoxin like 2A) Enables antioxidant activity. Involved in regulation of osteoclast differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.045978367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRXL2A	NM_032333.5	c.683A>G	p.Lys228Arg	missense_variant	Exon 6 of 6	ENST00000606162.6	NP_115709.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRXL2A	ENST00000606162.6	c.683A>G	p.Lys228Arg	missense_variant	Exon 6 of 6	1	NM_032333.5	ENSP00000482445.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.683A>G (p.K228R) alteration is located in exon 6 (coding exon 5) of the FAM213A gene. This alteration results from a A to G substitution at nucleotide position 683, causing the lysine (K) at amino acid position 228 to be replaced by an arginine (R). 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	0.070
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;T;T;.;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.47	.;.;.;T;T;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.046	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.25	N;.;.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;.;.;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;B
Vest4		0.11
MutPred		0.11		Loss of methylation at K228 (P = 0.028);Loss of methylation at K228 (P = 0.028);Loss of methylation at K228 (P = 0.028);.;Loss of methylation at K228 (P = 0.028);Loss of methylation at K228 (P = 0.028);
MVP		0.099
MPC		0.20
ClinPred		0.055	T
GERP RS		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.49

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: chr10-82191848;