Genetic Variant NM_001367770.1:c.813A>G (chrX-153398037-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001367770.1(PNMA6E):c.813A>G(p.Ala271Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 446,183 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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 0.00010 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 15 hem. )

Consequence

PNMA6E
NM_001367770.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.619

Publications

0 publications found

Variant links:

Genes affected

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

PNMA6E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-153398037-T-C is Benign according to our data. Variant chrX-153398037-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2661681.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.619 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367770.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNMA6E	NM_001367770.1	MANE Select	c.813A>G	p.Ala271Ala	synonymous	Exon 2 of 2	NP_001354699.1	A0A0J9YXQ4
PNMA6E	NM_001351293.2		c.144-165A>G		intron	N/A	NP_001338222.1	A0A0J9YXH5
PNMA6E	NM_001351294.2		c.144-165A>G		intron	N/A	NP_001338223.1	A0A0J9YXH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA6E	ENST00000445091.3	TSL:2 MANE Select	c.813A>G	p.Ala271Ala	synonymous	Exon 2 of 2	ENSP00000488500.1	A0A0J9YXQ4
	PNMA6E	ENST00000633844.1	TSL:3	c.144-165A>G		intron	N/A	ENSP00000488404.1	A0A0J9YXH5

Frequencies

GnomAD3 genomes

AF:

0.0000997

AC:

AN:

110338

Hom.:

Cov.:

show subpopulations

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:

0.000394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

AN:

335797

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

115295

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10085

American (AMR)

AF:

0.00

AC:

AN:

16360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10134

East Asian (EAS)

AF:

0.0000871

AC:

AN:

22955

South Asian (SAS)

AF:

0.000259

AC:

AN:

26980

European-Finnish (FIN)

AF:

0.000176

AC:

AN:

22728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1415

European-Non Finnish (NFE)

AF:

0.000142

AC:

AN:

204921

Other (OTH)

AF:

0.00

AC:

AN:

20219

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000997

AC:

AN:

110386

Hom.:

Cov.:

AF XY:

0.0000915

AC XY:

AN XY:

32782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30296

American (AMR)

AF:

0.00

AC:

AN:

10454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3485

South Asian (SAS)

AF:

0.000394

AC:

AN:

2535

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000190

AC:

AN:

52661

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.91

(source)

DANN

Benign

0.33

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over