chrX-152990316-C-G

Variant names:

• chrX-152990316-C-G
• rs782467318
• NM_001184924.2:c.1283G>C

Variant summary

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

The NM_001184924.2(PNMA5):​c.1283G>C​(p.Gly428Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,036,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: not found (cov: 24)
  • Exomes 𝑓: 0.0000087 (0 hom. 3 hem.)
• Consequence: PNMA5 NM_001184924.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.65
• Publications: 0 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=0.020982146).
• 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.1283G>C	p.Gly428Ala	missense	Exon 4 of 4	NP_001171853.1	Q96PV4
	PNMA5	NM_001103150.1		c.1283G>C	p.Gly428Ala	missense	Exon 2 of 2	NP_001096620.1	Q96PV4
	PNMA5	NM_001103151.1		c.1283G>C	p.Gly428Ala	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.1283G>C	p.Gly428Ala	missense	Exon 4 of 4	ENSP00000445775.1	Q96PV4
	PNMA5	ENST00000361887.5	TSL:1	c.1283G>C	p.Gly428Ala	missense	Exon 2 of 2	ENSP00000354834.5	Q96PV4
	PNMA5	ENST00000439251.3	TSL:1	c.1283G>C	p.Gly428Ala	missense	Exon 2 of 2	ENSP00000388850.1	Q96PV4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000640 AC: 8 AN: 125038 AF XY: 0.0000504

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000535

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000868 AC: 9 AN: 1036497 Hom.: 0 Cov.: 30 AF XY: 0.00000897 AC XY: 3 AN XY: 334289

African (AFR) AF: 0.0000420 AC: 1 AN: 23803

American (AMR) AF: 0.000361 AC: 8 AN: 22143

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14983

East Asian (EAS) AF: 0.00 AC: 0 AN: 29137

South Asian (SAS) AF: 0.00 AC: 0 AN: 43191

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38163

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3828

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 817943

Other (OTH) AF: 0.00 AC: 0 AN: 43306

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000503 AC: 6

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	0.063
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0020
DANN	Benign	0.46
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-3.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.88	N
REVEL	Benign	0.0060
Sift	Benign	1.0	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.25		Gain of helix (P = 0.0199)
MVP		0.12
MPC		0.10
ClinPred		0.021	T
GERP RS		-5.5
Varity_R		0.028
gMVP		0.21
Mutation Taster		=99/1	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: rs782467318; hg19: chrX-152158860;