chr1-37718788-A-G

Position:

• chr1-37718788-A-G

Variant summary

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

The NM_001099439.2(EPHA10):​c.2785T>C​(p.Phe929Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPHA10 NM_001099439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

EPHA10 (HGNC:19987): (EPH receptor A10) Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005 [PubMed 15777695]). See MIM 179610 for additional background on Eph receptors and ephrins.[supplied by OMIM, Mar 2008]

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=0.13637975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA10	NM_001099439.2	c.2785T>C	p.Phe929Leu	missense_variant	16/17	ENST00000373048.9	NP_001092909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA10	ENST00000373048.9	c.2785T>C	p.Phe929Leu	missense_variant	16/17	5	NM_001099439.2	ENSP00000362139.4
EPHA10	ENST00000432874.7	n.*686T>C		non_coding_transcript_exon_variant	12/16	5		ENSP00000436425.1
EPHA10	ENST00000432874.7	n.*686T>C		3_prime_UTR_variant	12/16	5		ENSP00000436425.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.2785T>C (p.F929L) alteration is located in exon 16 (coding exon 16) of the EPHA10 gene. This alteration results from a T to C substitution at nucleotide position 2785, causing the phenylalanine (F) at amino acid position 929 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.078
Sift	Benign	0.65	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0050	.;B
Vest4		0.18
MutPred		0.26		Loss of glycosylation at S930 (P = 0.0839);Loss of glycosylation at S930 (P = 0.0839);
MVP		0.72
MPC		0.18
ClinPred		0.73	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-38184460;