X-153397152-G-A

Variant names:

• chrX-153397152-G-A
• rs181450068
• NM_001367770.1:c.1698C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001367770.1(PNMA6E):​c.1698C>T​(p.Pro566Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 296,844 control chromosomes in the GnomAD database, including 2 homozygotes. There are 145 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (1 hom., 34 hem., cov: 25)
  • Exomes 𝑓: 0.0017 (1 hom. 111 hem.)
• Consequence: PNMA6E NM_001367770.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.154

Genes affected

PNMA6E (HGNC:50767): (PNMA family member 6E)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-153397152-G-A is Benign according to our data. Variant chrX-153397152-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.154 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNMA6E	NM_001367770.1	c.1698C>T	p.Pro566Pro	synonymous_variant	Exon 2 of 2	ENST00000445091.3	NP_001354699.1
PNMA6E	NM_001351293.2	c.864C>T	p.Pro288Pro	synonymous_variant	Exon 3 of 3		NP_001338222.1
PNMA6E	NM_001351294.2	c.864C>T	p.Pro288Pro	synonymous_variant	Exon 3 of 3		NP_001338223.1
PNMA6E	XM_047442374.1	c.1698C>T	p.Pro566Pro	synonymous_variant	Exon 2 of 2		XP_047298330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNMA6E	ENST00000445091.3	c.1698C>T	p.Pro566Pro	synonymous_variant	Exon 2 of 2	2	NM_001367770.1	ENSP00000488500.1
PNMA6E	ENST00000633844.1	c.864C>T	p.Pro288Pro	synonymous_variant	Exon 3 of 3	3		ENSP00000488404.1

Frequencies

GnomAD3 genomes AF: 0.000807 AC: 91 AN: 112801 Hom.: 1 Cov.: 25 AF XY: 0.000972 AC XY: 34 AN XY: 34965

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000277

Gnomad ASJ AF: 0.00452

Gnomad EAS AF: 0.00281

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.000656

GnomAD4 exome AF: 0.00172 AC: 317 AN: 183991 Hom.: 1 Cov.: 0 AF XY: 0.00178 AC XY: 111 AN XY: 62453

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000354

Gnomad4 ASJ exome AF: 0.00359

Gnomad4 EAS exome AF: 0.00660

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.000125

Gnomad4 NFE exome AF: 0.00123

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.000806 AC: 91 AN: 112853 Hom.: 1 Cov.: 25 AF XY: 0.000971 AC XY: 34 AN XY: 35027

Gnomad4 AFR AF: 0.0000320

Gnomad4 AMR AF: 0.000277

Gnomad4 ASJ AF: 0.00452

Gnomad4 EAS AF: 0.00281

Gnomad4 SAS AF: 0.00687

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000810

Gnomad4 OTH AF: 0.000648

Alfa AF: 0.000594 Hom.: 4

Bravo AF: 0.000661

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PNMA6E: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs181450068; hg19: chrX-152662610;