rs10077690

chr5-148409235-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_205836.3(FBXO38):c.962+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,472,562 control chromosomes in the GnomAD database, including 40,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3332 hom., cov: 32)
  • Exomes 𝑓: 0.24 (36689 hom.)
• Consequence: FBXO38 NM_205836.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.13

Genes affected

FBXO38 (HGNC:28844): (F-box protein 38) This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-148409235-A-G is Benign according to our data. Variant chr5-148409235-A-G is described in ClinVar as [Benign]. Clinvar id is 1235574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148409235-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO38	NM_205836.3	c.962+18A>G		intron_variant		ENST00000340253.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO38	ENST00000340253.10	c.962+18A>G		intron_variant		5	NM_205836.3	P3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31262 AN: 151896 Hom.: 3327 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.230 AC: 57852 AN: 251140 Hom.: 6909 AF XY: 0.232 AC XY: 31490 AN XY: 135744

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.235 AC: 310796 AN: 1320548 Hom.: 36689 Cov.: 20 AF XY: 0.235 AC XY: 156233 AN XY: 664606

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.206 AC: 31263 AN: 152014 Hom.: 3332 Cov.: 32 AF XY: 0.204 AC XY: 15169 AN XY: 74304

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.202

Alfa AF: 0.224 Hom.: 3908

Bravo AF: 0.202

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Distal hereditary motor neuropathy type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Neuronopathy, distal hereditary motor, type 2D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.027
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10077690; hg19: chr5-147788798; COSMIC: COSV57027953; COSMIC: COSV57027953;