5-148395099-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.128+195T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,082 control chromosomes in the GnomAD database, including 4,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (4799 hom., cov: 32)
• Consequence: FBXO38 NM_205836.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.465

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=-0.83).
• BP6: Variant 5-148395099-T-G is Benign according to our data. Variant chr5-148395099-T-G is described in ClinVar as [Benign]. Clinvar id is 1237618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO38	NM_205836.3	c.128+195T>G		intron_variant		ENST00000340253.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO38	ENST00000340253.10	c.128+195T>G		intron_variant		5	NM_205836.3	P3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38016 AN: 151964 Hom.: 4788 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.250 AC: 38052 AN: 152082 Hom.: 4799 Cov.: 32 AF XY: 0.248 AC XY: 18415 AN XY: 74328

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.239

Alfa AF: 0.131 Hom.: 224

Bravo AF: 0.248

Asia WGS AF: 0.254 AC: 882 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	-0.83
Cadd	Benign	2.7
Dann	Benign	0.36

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: rs10072051; hg19: chr5-147774662;