5-148427420-C-T

Variant names:

• chr5-148427420-C-T
• rs776182581
• NM_205836.3:c.2126C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_205836.3(FBXO38):​c.2126C>T​(p.Ala709Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO38 NM_205836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09124601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO38	NM_205836.3	c.2126C>T	p.Ala709Val	missense_variant	Exon 15 of 22	ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10	c.2126C>T	p.Ala709Val	missense_variant	Exon 15 of 22	5	NM_205836.3	ENSP00000342023.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250752 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135550

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.034	B;B
Vest4		0.29
MutPred		0.16		Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP		0.22
MPC		0.54
ClinPred		0.42	T
GERP RS		4.5
Varity_R		0.079
gMVP		0.25

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: rs776182581; hg19: chr5-147806983;