chr9-96651703-C-T

Variant names:

• chr9-96651703-C-T
• NM_153698.2:c.271G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153698.2(PRXL2C):​c.271G>A​(p.Val91Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRXL2C NM_153698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.527

Genes affected

PRXL2C (HGNC:16881): (peroxiredoxin like 2C) Predicted to enable antioxidant activity. Involved in positive regulation of ERK1 and ERK2 cascade and positive regulation of glycolytic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093345374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRXL2C	NM_153698.2	c.271G>A	p.Val91Ile	missense_variant	Exon 3 of 6	ENST00000375234.8	NP_714542.1
PRXL2C	XM_005251783.4	c.271G>A	p.Val91Ile	missense_variant	Exon 3 of 5		XP_005251840.1
PRXL2C	XM_005251784.5	c.109G>A	p.Val37Ile	missense_variant	Exon 3 of 6		XP_005251841.1
PRXL2C	XM_047422905.1	c.109G>A	p.Val37Ile	missense_variant	Exon 3 of 5		XP_047278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRXL2C	ENST00000375234.8	c.271G>A	p.Val91Ile	missense_variant	Exon 3 of 6	1	NM_153698.2	ENSP00000364382.3
PRXL2C	ENST00000446045.1	c.130G>A	p.Val44Ile	missense_variant	Exon 3 of 6	1		ENSP00000398933.1
PRXL2C	ENST00000411939.5	c.52G>A	p.Val18Ile	missense_variant	Exon 2 of 4	3		ENSP00000412378.1
PRXL2C	ENST00000464512.1	n.278G>A		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456366 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724608

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271G>A (p.V91I) alteration is located in exon 3 (coding exon 3) of the AAED1 gene. This alteration results from a G to A substitution at nucleotide position 271, causing the valine (V) at amino acid position 91 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.012
Sift	Benign	0.16	T
Sift4G	Benign	0.20	T
Polyphen		0.059	B
Vest4		0.22
MutPred		0.42		Gain of helix (P = 0.132);
MVP		0.16
MPC		0.025
ClinPred		0.31	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.32

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: chr9-99413985;