12-6326587-G-A

Variant summary

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

The NM_001384598.1(PLEKHG6):​c.1670+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,450,664 control chromosomes in the GnomAD database, including 151,579 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 0.35 ( 11773 hom., cov: 31)
Exomes 𝑓: 0.46 ( 139806 hom. )

Consequence

PLEKHG6
NM_001384598.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570
Variant links:
Genes affected
PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHG6NM_001384598.1 linkuse as main transcriptc.1670+14G>A intron_variant ENST00000684764.1 NP_001371527.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHG6ENST00000684764.1 linkuse as main transcriptc.1670+14G>A intron_variant NM_001384598.1 ENSP00000506982 P1Q3KR16-1

Frequencies

GnomAD3 genomes
AF:
0.353
AC:
53583
AN:
151964
Hom.:
11775
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.100
Gnomad AMI
AF:
0.409
Gnomad AMR
AF:
0.345
Gnomad ASJ
AF:
0.409
Gnomad EAS
AF:
0.184
Gnomad SAS
AF:
0.316
Gnomad FIN
AF:
0.586
Gnomad MID
AF:
0.357
Gnomad NFE
AF:
0.484
Gnomad OTH
AF:
0.338
GnomAD3 exomes
AF:
0.407
AC:
54549
AN:
133974
Hom.:
11911
AF XY:
0.415
AC XY:
30514
AN XY:
73596
show subpopulations
Gnomad AFR exome
AF:
0.104
Gnomad AMR exome
AF:
0.325
Gnomad ASJ exome
AF:
0.402
Gnomad EAS exome
AF:
0.190
Gnomad SAS exome
AF:
0.324
Gnomad FIN exome
AF:
0.569
Gnomad NFE exome
AF:
0.477
Gnomad OTH exome
AF:
0.411
GnomAD4 exome
AF:
0.456
AC:
592345
AN:
1298582
Hom.:
139806
Cov.:
32
AF XY:
0.455
AC XY:
289966
AN XY:
637886
show subpopulations
Gnomad4 AFR exome
AF:
0.0880
Gnomad4 AMR exome
AF:
0.311
Gnomad4 ASJ exome
AF:
0.397
Gnomad4 EAS exome
AF:
0.224
Gnomad4 SAS exome
AF:
0.334
Gnomad4 FIN exome
AF:
0.574
Gnomad4 NFE exome
AF:
0.482
Gnomad4 OTH exome
AF:
0.416
GnomAD4 genome
AF:
0.352
AC:
53586
AN:
152082
Hom.:
11773
Cov.:
31
AF XY:
0.357
AC XY:
26538
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.100
Gnomad4 AMR
AF:
0.344
Gnomad4 ASJ
AF:
0.409
Gnomad4 EAS
AF:
0.184
Gnomad4 SAS
AF:
0.316
Gnomad4 FIN
AF:
0.586
Gnomad4 NFE
AF:
0.484
Gnomad4 OTH
AF:
0.340
Alfa
AF:
0.359
Hom.:
3103
Bravo
AF:
0.318
Asia WGS
AF:
0.263
AC:
914
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
4.1
DANN
Benign
0.71

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: rs2302350; hg19: chr12-6435753; COSMIC: COSV50610025; COSMIC: COSV50610025; API