5-148433338-T-G

Position:

• chr5-148433338-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_205836.3(FBXO38):​c.2654-86T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 855,618 control chromosomes in the GnomAD database, including 54,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15845 hom., cov: 32)
  • Exomes 𝑓: 0.32 (39145 hom.)
• Consequence: FBXO38 NM_205836.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-148433338-T-G is Benign according to our data. Variant chr5-148433338-T-G is described in ClinVar as [Benign]. Clinvar id is 1223057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO38	NM_205836.3	c.2654-86T>G		intron_variant		ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10	c.2654-86T>G		intron_variant		5	NM_205836.3	ENSP00000342023	P3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63743 AN: 151940 Hom.: 15795 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.318 AC: 223608 AN: 703560 Hom.: 39145 Cov.: 9 AF XY: 0.319 AC XY: 117858 AN XY: 369768

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.420 AC: 63849 AN: 152058 Hom.: 15845 Cov.: 32 AF XY: 0.419 AC XY: 31137 AN XY: 74336

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.390

Alfa AF: 0.361 Hom.: 2387

Bravo AF: 0.436

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.91
CADD	Benign	0.89
DANN	Benign	0.77

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: rs6861078; hg19: chr5-147812901; COSMIC: COSV57032618; COSMIC: COSV57032618;