rs3007421

Variant names:

• chr1-6470129-G-A
• rs3007421
• NM_020631.6:c.1800+107C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6470129-G-A
• chr1-6470129-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020631.6(PLEKHG5):​c.1800+107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,258,266 control chromosomes in the GnomAD database, including 13,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2974 hom., cov: 33)
  • Exomes 𝑓: 0.13 (10059 hom.)
• Consequence: PLEKHG5 NM_020631.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.956
• Publications: 36 publications found

Genes affected

PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

PLEKHG5 Gene-Disease associations (from GenCC):

• neuromuscular disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease recessive intermediate C

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• neuronopathy, distal hereditary motor, autosomal recessive 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-6470129-G-A is Benign according to our data. Variant chr1-6470129-G-A is described in ClinVar as Benign. ClinVar VariationId is 667938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG5	NM_020631.6	MANE Select	c.1800+107C>T		intron	N/A	NP_065682.2
	PLEKHG5	NM_001265593.2		c.2007+107C>T		intron	N/A	NP_001252522.1	A0A804EMX3
	PLEKHG5	NM_001042663.3		c.1911+107C>T		intron	N/A	NP_001036128.2	O94827-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG5	ENST00000377728.8	TSL:2 MANE Select	c.1800+107C>T		intron	N/A	ENSP00000366957.3	O94827-5
	PLEKHG5	ENST00000377732.5	TSL:1	c.1911+107C>T		intron	N/A	ENSP00000366961.1	O94827-3
	PLEKHG5	ENST00000400915.8	TSL:1	c.1911+107C>T		intron	N/A	ENSP00000383706.4	O94827-3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26812 AN: 152064 Hom.: 2961 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.126 AC: 139643 AN: 1106084 Hom.: 10059 AF XY: 0.127 AC XY: 70912 AN XY: 557104

African (AFR) AF: 0.315 AC: 8157 AN: 25862

American (AMR) AF: 0.0826 AC: 2979 AN: 36066

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2470 AN: 20248

East Asian (EAS) AF: 0.00784 AC: 296 AN: 37770

South Asian (SAS) AF: 0.150 AC: 10513 AN: 69900

European-Finnish (FIN) AF: 0.110 AC: 4459 AN: 40604

Middle Eastern (MID) AF: 0.173 AC: 808 AN: 4680

European-Non Finnish (NFE) AF: 0.126 AC: 103454 AN: 822824

Other (OTH) AF: 0.135 AC: 6507 AN: 48130

GnomAD4 genome AF: 0.177 AC: 26867 AN: 152182 Hom.: 2974 Cov.: 33 AF XY: 0.175 AC XY: 13029 AN XY: 74398

African (AFR) AF: 0.318 AC: 13194 AN: 41478

American (AMR) AF: 0.126 AC: 1927 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5174

South Asian (SAS) AF: 0.155 AC: 748 AN: 4822

European-Finnish (FIN) AF: 0.102 AC: 1084 AN: 10618

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8958 AN: 68008

Other (OTH) AF: 0.166 AC: 351 AN: 2110

Alfa AF: 0.136 Hom.: 2019

Bravo AF: 0.183

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.49
PhyloP100		0.96
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: rs3007421; hg19: chr1-6530189;