chrX-152990391-C-T

Variant names:

• chrX-152990391-C-T
• NM_001184924.2:c.1208G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001184924.2(PNMA5):​c.1208G>A​(p.Gly403Glu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: PNMA5 NM_001184924.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.165

Genes affected

PNMA5 (HGNC:18743): (PNMA family member 5) This gene encodes a member of the paraneoplastic Ma antigen protein family. These proteins have been implicated in the development of paraneoplastic disorders resulting from an immune response directed against them. Paraneoplastic disorders are the result of an abnormal immune response to a tumor. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03656131).
• BP6: Variant X-152990391-C-T is Benign according to our data. Variant chrX-152990391-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3421610.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNMA5	NM_001184924.2	c.1208G>A	p.Gly403Glu	missense_variant	Exon 4 of 4	ENST00000535214.6	NP_001171853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNMA5	ENST00000535214.6	c.1208G>A	p.Gly403Glu	missense_variant	Exon 4 of 4	3	NM_001184924.2	ENSP00000445775.1
PNMA5	ENST00000361887.5	c.1208G>A	p.Gly403Glu	missense_variant	Exon 2 of 2	1		ENSP00000354834.5
PNMA5	ENST00000439251.3	c.1208G>A	p.Gly403Glu	missense_variant	Exon 2 of 2	1		ENSP00000388850.1
PNMA5	ENST00000452693.5	c.1208G>A	p.Gly403Glu	missense_variant	Exon 3 of 3	2		ENSP00000392342.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 07, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.067
DANN	Benign	0.53
DEOGEN2	Benign	0.0055	T;T;T;T
FATHMM_MKL	Benign	0.000080	N
LIST_S2	Benign	0.25	.;.;T;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.85	N;N;N;N
REVEL	Benign	0.011
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.051
MutPred		0.15		Loss of MoRF binding (P = 0.0441);Loss of MoRF binding (P = 0.0441);Loss of MoRF binding (P = 0.0441);Loss of MoRF binding (P = 0.0441);
MVP		0.085
MPC		0.12
ClinPred		0.033	T
GERP RS		0.49
Varity_R		0.050
gMVP		0.12

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: chrX-152158935;