8-26507774-T-A

Position:

• chr8-26507774-T-A

Variant summary

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

The NM_007257.6(PNMA2):​c.982A>T​(p.Met328Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNMA2 NM_007257.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

Genes affected

PNMA2 (HGNC:9159): (PNMA family member 2) Predicted to be involved in positive regulation of apoptotic process. Predicted to be located in nucleolus. [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=0.10057369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMA2	NM_007257.6	c.982A>T	p.Met328Leu	missense_variant	3/3	ENST00000522362.7	NP_009188.1
PNMA2	XM_011544365.4	c.982A>T	p.Met328Leu	missense_variant	3/3		XP_011542667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMA2	ENST00000522362.7	c.982A>T	p.Met328Leu	missense_variant	3/3	1	NM_007257.6	ENSP00000429344.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Nov 27, 2024

The c.982A>T (p.M328L) alteration is located in exon 3 (coding exon 1) of the PNMA2 gene. This alteration results from a A to T substitution at nucleotide position 982, causing the methionine (M) at amino acid position 328 to be replaced by a leucine (L). 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	0.24
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.80
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.37	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.012	B
Vest4		0.46
MutPred		0.42		Gain of methylation at K329 (P = 0.0303);
MVP		0.23
MPC		0.29
ClinPred		0.077	T
GERP RS		3.2
Varity_R		0.11
gMVP		0.18

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: chr8-26365290;