rs9434795

Variant names:

• chr1-6492439-T-C
• rs9434795
• ENST00000377732.5:c.24+4054A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-6492439-T-C
• chr1-6492439-T-G

Variant summary

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

The ENST00000377732.5(PLEKHG5):​c.24+4054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,964 control chromosomes in the GnomAD database, including 11,264 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 0.30 (11264 hom., cov: 32)
• Consequence: PLEKHG5 ENST00000377732.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 8 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuronopathy, distal hereditary motor, autosomal recessive 4

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

ENSG00000299237 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG5	NM_001042663.3	c.24+4054A>G		intron_variant	Intron 2 of 21		NP_001036128.2
PLEKHG5	NM_001265592.2	c.24+4054A>G		intron_variant	Intron 2 of 21		NP_001252521.2
PLEKHG5	NM_198681.4	c.-88+4054A>G		intron_variant	Intron 2 of 21		NP_941374.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG5	ENST00000377732.5	c.24+4054A>G		intron_variant	Intron 1 of 20	1		ENSP00000366961.1
PLEKHG5	ENST00000400915.8	c.24+4054A>G		intron_variant	Intron 2 of 21	1		ENSP00000383706.4
PLEKHG5	ENST00000377740.5	c.-88+4054A>G		intron_variant	Intron 2 of 21	1		ENSP00000366969.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45037 AN: 151846 Hom.: 11203 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.297 AC: 45162 AN: 151964 Hom.: 11264 Cov.: 32 AF XY: 0.298 AC XY: 22114 AN XY: 74268

African (AFR) AF: 0.686 AC: 28418 AN: 41404

American (AMR) AF: 0.187 AC: 2849 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1536 AN: 5156

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4812

European-Finnish (FIN) AF: 0.169 AC: 1786 AN: 10588

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.122 AC: 8263 AN: 67956

Other (OTH) AF: 0.256 AC: 538 AN: 2104

Alfa AF: 0.183 Hom.: 5968

Bravo AF: 0.315

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.55
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9434795; hg19: chr1-6552499;