rs1695770

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000247226.13(PLEKHG3):​c.*4745C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,144 control chromosomes in the GnomAD database, including 3,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3877 hom., cov: 32)
Exomes 𝑓: 0.23 ( 1 hom. )

Consequence

PLEKHG3
ENST00000247226.13 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33
Variant links:
Genes affected
PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHG3NM_001308147.2 linkuse as main transcriptc.*4745C>T 3_prime_UTR_variant 17/17 ENST00000247226.13 NP_001295076.1
SPTBNM_001355436.2 linkuse as main transcriptc.*858G>A 3_prime_UTR_variant 36/36 ENST00000644917.1 NP_001342365.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHG3ENST00000247226.13 linkuse as main transcriptc.*4745C>T 3_prime_UTR_variant 17/171 NM_001308147.2 ENSP00000247226 A2A1L390-1
SPTBENST00000644917.1 linkuse as main transcriptc.*858G>A 3_prime_UTR_variant 36/36 NM_001355436.2 ENSP00000495909 P1P11277-2
PLEKHG3ENST00000634379.2 linkuse as main transcriptc.*4745C>T 3_prime_UTR_variant 17/171 ENSP00000489373 P4
SPTBENST00000389722.7 linkuse as main transcriptc.*858G>A 3_prime_UTR_variant 35/352 ENSP00000374372 P1P11277-2

Frequencies

GnomAD3 genomes
AF:
0.210
AC:
31981
AN:
151964
Hom.:
3873
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.328
Gnomad AMI
AF:
0.103
Gnomad AMR
AF:
0.130
Gnomad ASJ
AF:
0.131
Gnomad EAS
AF:
0.0486
Gnomad SAS
AF:
0.186
Gnomad FIN
AF:
0.194
Gnomad MID
AF:
0.0924
Gnomad NFE
AF:
0.180
Gnomad OTH
AF:
0.185
GnomAD4 exome
AF:
0.226
AC:
14
AN:
62
Hom.:
1
Cov.:
0
AF XY:
0.238
AC XY:
10
AN XY:
42
show subpopulations
Gnomad4 FIN exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.185
GnomAD4 genome
AF:
0.211
AC:
32015
AN:
152082
Hom.:
3877
Cov.:
32
AF XY:
0.210
AC XY:
15583
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.328
Gnomad4 AMR
AF:
0.130
Gnomad4 ASJ
AF:
0.131
Gnomad4 EAS
AF:
0.0486
Gnomad4 SAS
AF:
0.187
Gnomad4 FIN
AF:
0.194
Gnomad4 NFE
AF:
0.180
Gnomad4 OTH
AF:
0.184
Alfa
AF:
0.176
Hom.:
2291
Bravo
AF:
0.207
Asia WGS
AF:
0.167
AC:
584
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.18
DANN
Benign
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1695770; hg19: chr14-65215166; API