GeneBe

12-19257427-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001256470.2(PLEKHA5):​c.433-6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000077 in 1,298,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

PLEKHA5
NM_001256470.2 splice_region, intron

Scores

2
Splicing: ADA: 0.00001543
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.101

Publications

0 publications found
Variant links:
Genes affected
PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHA5NM_001256470.2 linkc.433-6A>T splice_region_variant, intron_variant Intron 5 of 31 ENST00000429027.7 NP_001243399.1 Q9HAU0-6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLEKHA5ENST00000429027.7 linkc.433-6A>T splice_region_variant, intron_variant Intron 5 of 31 1 NM_001256470.2 ENSP00000404296.2 Q9HAU0-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.70e-7
AC:
1
AN:
1298254
Hom.:
0
Cov.:
19
AF XY:
0.00000153
AC XY:
1
AN XY:
653568
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
29342
American (AMR)
AF:
0.00
AC:
0
AN:
41276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24836
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38558
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78970
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53176
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5386
European-Non Finnish (NFE)
AF:
0.00000103
AC:
1
AN:
972036
Other (OTH)
AF:
0.00
AC:
0
AN:
54674
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.090
DANN
Benign
0.81
PhyloP100
-0.10

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000015
dbscSNV1_RF
Benign
0.0
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

Other links and lift over

dbSNP: rs200644310; hg19: chr12-19410361; API