rs3734120

chr5-148441906-C-T

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.3389-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,423,262 control chromosomes in the GnomAD database, including 50,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5334 hom., cov: 32)
  • Exomes 𝑓: 0.27 (45569 hom.)
• Consequence: FBXO38 NM_205836.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489

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=-0.74).
• BP6: Variant 5-148441906-C-T is Benign according to our data. Variant chr5-148441906-C-T is described in ClinVar as [Benign]. Clinvar id is 1250411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO38	NM_205836.3	c.3389-63C>T		intron_variant		ENST00000340253.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO38	ENST00000340253.10	c.3389-63C>T		intron_variant		5	NM_205836.3	P3
FBXO38	ENST00000394370.7	c.3164-63C>T		intron_variant		1		A1
FBXO38	ENST00000513826.1	c.2654-63C>T		intron_variant		1		A1
FBXO38	ENST00000296701.10	c.2654-63C>T		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40012 AN: 151966 Hom.: 5323 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.266 AC: 337932 AN: 1271184 Hom.: 45569 AF XY: 0.267 AC XY: 168729 AN XY: 633068

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.263 AC: 40052 AN: 152078 Hom.: 5334 Cov.: 32 AF XY: 0.260 AC XY: 19335 AN XY: 74338

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.248

Alfa AF: 0.265 Hom.: 1112

Bravo AF: 0.264

Asia WGS AF: 0.257 AC: 894 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	-0.74
Cadd	Benign	6.1
Dann	Benign	0.63

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: rs3734120; hg19: chr5-147821469; COSMIC: COSV57026539; COSMIC: COSV57026539;