14-64745677-A-G

Variant names:

• chr14-64745677-A-G
• rs229648
• NM_001308147.2:c.*1974A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308147.2(PLEKHG3):​c.*1974A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,286 control chromosomes in the GnomAD database, including 1,635 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 0.14 (1635 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: PLEKHG3 NM_001308147.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308147.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG3	NM_001308147.2	MANE Select	c.*1974A>G		3_prime_UTR	Exon 17 of 17	NP_001295076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG3	ENST00000247226.13	TSL:1 MANE Select	c.*1974A>G		3_prime_UTR	Exon 17 of 17	ENSP00000247226.8
	PLEKHG3	ENST00000634379.2	TSL:1	c.*1974A>G		3_prime_UTR	Exon 17 of 17	ENSP00000489373.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20814 AN: 152162 Hom.: 1638 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.137 AC: 20825 AN: 152280 Hom.: 1635 Cov.: 32 AF XY: 0.135 AC XY: 10027 AN XY: 74464

African (AFR) AF: 0.201 AC: 8361 AN: 41540

American (AMR) AF: 0.101 AC: 1551 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.00751 AC: 39 AN: 5190

South Asian (SAS) AF: 0.142 AC: 684 AN: 4830

European-Finnish (FIN) AF: 0.0969 AC: 1029 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8412 AN: 68012

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.121 Hom.: 2247

Bravo AF: 0.137

Asia WGS AF: 0.0960 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs229648; hg19: chr14-65212395;