2-208015527-C-T

Variant names:

• chr2-208015527-C-T
• rs6712527
• NM_001080475.3:c.-319+9862G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000427836.8(PLEKHM3):​c.-319+9862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,054 control chromosomes in the GnomAD database, including 29,454 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 0.59 (29454 hom., cov: 32)
• Consequence: PLEKHM3 ENST00000427836.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839
• Publications: 3 publications found

Genes affected

PLEKHM3 (HGNC:34006): (pleckstrin homology domain containing M3) Predicted to enable metal ion binding activity. Predicted to be involved in myoblast differentiation. Predicted to be located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309739 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427836.8. 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
	PLEKHM3	NM_001080475.3	MANE Select	c.-319+9862G>A		intron	N/A	NP_001073944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHM3	ENST00000427836.8	TSL:5 MANE Select	c.-319+9862G>A		intron	N/A	ENSP00000417003.2
	PLEKHM3	ENST00000457206.1	TSL:1	c.-319+9862G>A		intron	N/A	ENSP00000400150.1
	ENSG00000309739	ENST00000843626.1		n.147+559C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89959 AN: 151936 Hom.: 29433 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 90021 AN: 152054 Hom.: 29454 Cov.: 32 AF XY: 0.592 AC XY: 43958 AN XY: 74298

African (AFR) AF: 0.306 AC: 12684 AN: 41442

American (AMR) AF: 0.672 AC: 10265 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2651 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2394 AN: 5172

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4820

European-Finnish (FIN) AF: 0.743 AC: 7842 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49620 AN: 67990

Other (OTH) AF: 0.599 AC: 1267 AN: 2114

Alfa AF: 0.586 Hom.: 1434

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.84
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: rs6712527; hg19: chr2-208880251;