X-152990474-G-C

Variant names:

• chrX-152990474-G-C
• rs369163473
• NM_001184924.2:c.1125C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001184924.2(PNMA5):​c.1125C>G​(p.Ser375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,171,897 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 10 hem.)
• Consequence: PNMA5 NM_001184924.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.08
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034510463).
• BS2: High Hemizygotes in GnomAdExome4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184924.2. 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
	PNMA5	NM_001184924.2	MANE Select	c.1125C>G	p.Ser375Arg	missense	Exon 4 of 4	NP_001171853.1	Q96PV4
	PNMA5	NM_001103150.1		c.1125C>G	p.Ser375Arg	missense	Exon 2 of 2	NP_001096620.1	Q96PV4
	PNMA5	NM_001103151.1		c.1125C>G	p.Ser375Arg	missense	Exon 3 of 3	NP_001096621.1	Q96PV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA5	ENST00000535214.6	TSL:3 MANE Select	c.1125C>G	p.Ser375Arg	missense	Exon 4 of 4	ENSP00000445775.1	Q96PV4
	PNMA5	ENST00000361887.5	TSL:1	c.1125C>G	p.Ser375Arg	missense	Exon 2 of 2	ENSP00000354834.5	Q96PV4
	PNMA5	ENST00000439251.3	TSL:1	c.1125C>G	p.Ser375Arg	missense	Exon 2 of 2	ENSP00000388850.1	Q96PV4

Frequencies

GnomAD3 genomes AF: 0.00000889 AC: 1 AN: 112427 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000687 AC: 1 AN: 145665 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000147

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000208 AC: 22 AN: 1059470 Hom.: 0 Cov.: 31 AF XY: 0.0000292 AC XY: 10 AN XY: 342094

African (AFR) AF: 0.00 AC: 0 AN: 24708

American (AMR) AF: 0.0000366 AC: 1 AN: 27288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16733

East Asian (EAS) AF: 0.00 AC: 0 AN: 29890

South Asian (SAS) AF: 0.00 AC: 0 AN: 47604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3933

European-Non Finnish (NFE) AF: 0.0000254 AC: 21 AN: 825651

Other (OTH) AF: 0.00 AC: 0 AN: 44319

GnomAD4 genome AF: 0.00000889 AC: 1 AN: 112427 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34579

African (AFR) AF: 0.00 AC: 0 AN: 30953

American (AMR) AF: 0.00 AC: 0 AN: 10701

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3566

South Asian (SAS) AF: 0.00 AC: 0 AN: 2721

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53217

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.022
DANN	Benign	0.57
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.00046	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-3.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.012
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.23		Loss of phosphorylation at S375 (P = 0.014)
MVP		0.076
MPC		0.10
ClinPred		0.025	T
GERP RS		-5.4
Varity_R		0.085
gMVP		0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs369163473; hg19: chrX-152159018;