rs3734120

Variant names:

• chr5-148441906-C-T
• rs3734120
• NM_205836.3:c.3389-63C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

FBXO38 Gene-Disease associations (from GenCC):

• neuronopathy, distal hereditary motor, type 2D

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• distal hereditary motor neuropathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• distal hereditary motor neuropathy type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FBXO38	NM_205836.3	c.3389-63C>T		intron_variant	Intron 21 of 21	ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10	c.3389-63C>T		intron_variant	Intron 21 of 21	5	NM_205836.3	ENSP00000342023.6
FBXO38	ENST00000394370.7	c.3164-63C>T		intron_variant	Intron 21 of 21	1		ENSP00000377895.3
FBXO38	ENST00000513826.1	c.2654-63C>T		intron_variant	Intron 19 of 19	1		ENSP00000426410.1
FBXO38	ENST00000296701.10	c.2654-63C>T		intron_variant	Intron 20 of 20	2		ENSP00000296701.6

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

African (AFR) AF: 0.276 AC: 8102 AN: 29334

American (AMR) AF: 0.281 AC: 10501 AN: 37392

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4116 AN: 21552

East Asian (EAS) AF: 0.196 AC: 7420 AN: 37880

South Asian (SAS) AF: 0.292 AC: 21104 AN: 72198

European-Finnish (FIN) AF: 0.234 AC: 10180 AN: 43596

Middle Eastern (MID) AF: 0.269 AC: 1403 AN: 5218

European-Non Finnish (NFE) AF: 0.269 AC: 261391 AN: 970308

Other (OTH) AF: 0.255 AC: 13715 AN: 53706

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

African (AFR) AF: 0.274 AC: 11353 AN: 41454

American (AMR) AF: 0.258 AC: 3936 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1244 AN: 5176

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2415 AN: 10584

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.269 AC: 18320 AN: 67980

Other (OTH) AF: 0.248 AC: 525 AN: 2114

Alfa AF: 0.264 Hom.: 1139

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

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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