Genetic Variant NM_001329630.2:c.3630C>T (chr11-16783720-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001329630.2(PLEKHA7):c.3630C>T(p.Arg1210Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,478,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00063 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0530

Publications

1 publications found

Variant links:

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA7 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 11-16783720-G-A is Benign according to our data. Variant chr11-16783720-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3047626.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.053 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329630.2. 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
	PLEKHA7	NM_001329630.2	MANE Select	c.3630C>T	p.Arg1210Arg	synonymous	Exon 25 of 27	NP_001316559.1	E9PKC0
	PLEKHA7	NM_001410960.1		c.3633C>T	p.Arg1211Arg	synonymous	Exon 25 of 27	NP_001397889.1	A0A8V8TMS3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHA7	ENST00000531066.6	TSL:5 MANE Select	c.3630C>T	p.Arg1210Arg	synonymous	Exon 25 of 27	ENSP00000435389.1	E9PKC0
PLEKHA7	ENST00000698836.1		c.3633C>T	p.Arg1211Arg	synonymous	Exon 25 of 27	ENSP00000513972.1	A0A8V8TMS3
PLEKHA7	ENST00000917925.1		c.3474C>T	p.Arg1158Arg	synonymous	Exon 24 of 26	ENSP00000587984.1

Frequencies

GnomAD3 genomes

AF:

0.000630

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.000131

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:

0.000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000363

AC:

AN:

88160

AF XY:

0.000372

show subpopulations

Gnomad AFR exome

AF:

0.000784

Gnomad AMR exome

AF:

0.000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000621

Gnomad OTH exome

AF:

0.000373

GnomAD4 exome

AF:

0.000563

AC:

747

AN:

1326464

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

353

AN XY:

652186

show subpopulations

African (AFR)

AF:

0.000208

AC:

AN:

28780

American (AMR)

AF:

0.000360

AC:

AN:

27750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22942

East Asian (EAS)

AF:

0.00

AC:

AN:

31802

South Asian (SAS)

AF:

0.0000569

AC:

AN:

70314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32862

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.000667

AC:

701

AN:

1051000

Other (OTH)

AF:

0.000450

AC:

AN:

55532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000630

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41478

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000470

Hom.:

Bravo

AF:

0.000774

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLEKHA7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

7.3

(source)

DANN

Benign

0.76

PhyloP100

0.053

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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