chr9-96646001-T-A

Variant names:

• chr9-96646001-T-A
• rs764147841
• NM_153698.2:c.445A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153698.2(PRXL2C):​c.445A>T​(p.Asn149Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,922 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N149D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRXL2C NM_153698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.16
• Publications: 2 publications found

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]

ENSG00000294376 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153698.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2C	NM_153698.2	MANE Select	c.445A>T	p.Asn149Tyr	missense	Exon 5 of 6	NP_714542.1	Q7RTV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRXL2C	ENST00000375234.8	TSL:1 MANE Select	c.445A>T	p.Asn149Tyr	missense	Exon 5 of 6	ENSP00000364382.3	Q7RTV5
	PRXL2C	ENST00000446045.1	TSL:1	c.304A>T	p.Asn102Tyr	missense	Exon 5 of 6	ENSP00000398933.1	H0Y5J5
	PRXL2C	ENST00000946150.1		c.445A>T	p.Asn149Tyr	missense	Exon 5 of 6	ENSP00000616209.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459922 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726250

African (AFR) AF: 0.00 AC: 0 AN: 33322

American (AMR) AF: 0.00 AC: 0 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111444

Other (OTH) AF: 0.00 AC: 0 AN: 60284

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.91	T
PhyloP100		5.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.081
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.024	D
Polyphen		0.051	B
Vest4		0.78
MutPred		0.46		Loss of solvent accessibility (P = 0.0193)
MVP		0.30
MPC		0.032
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.44
gMVP		0.59
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs764147841; hg19: chr9-99408283;