10-129842123-G-T

Variant names:

• chr10-129842123-G-T
• rs200954762
• NM_001375380.1:c.1365C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001375380.1(EBF3):​c.1365C>A​(p.Asn455Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N455N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBF3 NM_001375380.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

Genes affected

EBF3 (HGNC:19087): (EBF transcription factor 3) This gene encodes a member of the early B-cell factor (EBF) family of DNA binding transcription factors. EBF proteins are involved in B-cell differentiation, bone development and neurogenesis, and may also function as tumor suppressors. The encoded protein inhibits cell survival through the regulation of genes involved in cell cycle arrest and apoptosis, and aberrant methylation or deletion of this gene may play a role in multiple malignancies including glioblastoma multiforme and gastric carcinoma. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the EBF3 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 40 curated pathogenic missense variants (we use a threshold of 10). The gene has 6 curated benign missense variants. Gene score misZ: 3.6113 (above the threshold of 3.09). Trascript score misZ: 3.1409 (above the threshold of 3.09). GenCC associations: The gene is linked to hypotonia, ataxia, and delayed development syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.1365C>A	p.Asn455Lys	missense_variant	Exon 13 of 17	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.1365C>A	p.Asn455Lys	missense_variant	Exon 13 of 17	3	NM_001375380.1	ENSP00000387543.2
EBF3	ENST00000368648.8	c.1338C>A	p.Asn446Lys	missense_variant	Exon 14 of 17	1		ENSP00000357637.3
EBF3	ENST00000355311.10	c.1365C>A	p.Asn455Lys	missense_variant	Exon 13 of 16	5		ENSP00000347463.4
EBF3	ENST00000675373.1	n.1010C>A		non_coding_transcript_exon_variant	Exon 10 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Uncertain	0.43	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L
PhyloP100		-0.54
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.091
Sift	Benign	0.13	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.25	B;.
Vest4		0.76
MutPred		0.34		Gain of ubiquitination at N446 (P = 0.0011);.;
MVP		0.33
MPC		0.77
ClinPred		0.64	D
GERP RS		-4.1
Varity_R		0.20
gMVP		0.76
Mutation Taster		=67/33	polymorphism

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs200954762; hg19: chr10-131640387;