rs17054320

Variant names:

• chr6-150841717-T-A
• rs17054320
• NM_001029884.3:c.*821T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150841717-T-A
• chr6-150841717-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001029884.3(PLEKHG1):​c.*821T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,316 control chromosomes in the GnomAD database, including 95 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 0.033 (95 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHG1 NM_001029884.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 6 publications found

Genes affected

PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0329 (5017/152316) while in subpopulation SAS AF = 0.055 (265/4822). AF 95% confidence interval is 0.0495. There are 95 homozygotes in GnomAd4. There are 2340 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5017 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.*821T>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.*821T>A		3_prime_UTR_variant	Exon 17 of 17		NM_001029884.3	ENSP00000512689.1
PLEKHG1	ENST00000475490.1	n.*80-122T>A		intron_variant	Intron 14 of 14	1		ENSP00000433107.1
PLEKHG1	ENST00000358517.6	c.*821T>A		3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000351318.2
PLEKHG1	ENST00000644968.1	c.*821T>A		3_prime_UTR_variant	Exon 16 of 16			ENSP00000496254.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5004 AN: 152198 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0373

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0329 AC: 5017 AN: 152316 Hom.: 95 Cov.: 33 AF XY: 0.0314 AC XY: 2340 AN XY: 74488

African (AFR) AF: 0.0206 AC: 855 AN: 41580

American (AMR) AF: 0.0279 AC: 426 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5190

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4822

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2838 AN: 68020

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0152 Hom.: 5

Bravo AF: 0.0324

Asia WGS AF: 0.0590 AC: 204 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	4.2
DANN	Benign	0.41
PhyloP100		1.4
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: rs17054320; hg19: chr6-151162853;