X-152990474-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001184924.2(PNMA5):​c.1125C>T​(p.Ser375Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,171,894 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: PNMA5 NM_001184924.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-3.08 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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>T	p.Ser375Ser	synonymous	Exon 4 of 4	NP_001171853.1	Q96PV4
	PNMA5	NM_001103150.1		c.1125C>T	p.Ser375Ser	synonymous	Exon 2 of 2	NP_001096620.1	Q96PV4
	PNMA5	NM_001103151.1		c.1125C>T	p.Ser375Ser	synonymous	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>T	p.Ser375Ser	synonymous	Exon 4 of 4	ENSP00000445775.1	Q96PV4
	PNMA5	ENST00000361887.5	TSL:1	c.1125C>T	p.Ser375Ser	synonymous	Exon 2 of 2	ENSP00000354834.5	Q96PV4
	PNMA5	ENST00000439251.3	TSL:1	c.1125C>T	p.Ser375Ser	synonymous	Exon 2 of 2	ENSP00000388850.1	Q96PV4

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 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: 0.000280

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 3 AN: 145665 AF XY: 0.0000216

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: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 11 AN: 1059467 Hom.: 0 Cov.: 31 AF XY: 0.00000877 AC XY: 3 AN XY: 342091

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

American (AMR) AF: 0.0000366 AC: 1 AN: 27287

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

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

South Asian (SAS) AF: 0.0000210 AC: 1 AN: 47603

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39343

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

European-Non Finnish (NFE) AF: 0.0000109 AC: 9 AN: 825651

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

GnomAD4 genome AF: 0.0000267 AC: 3 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: 0.000280 AC: 1 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: 0.0000376 AC: 2 AN: 53217

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.69
PhyloP100		-3.1
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;