11-62605736-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_153265.3(EML3):​c.1820C>T​(p.Pro607Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EML3
NM_153265.3 missense

Scores

13
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.95
Variant links:
Genes affected
EML3 (HGNC:26666): (EMAP like 3) Predicted to enable microtubule binding activity. Involved in mitotic metaphase plate congression and regulation of mitotic spindle assembly. Located in several cellular components, including midbody; mitotic spindle microtubule; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EML3NM_153265.3 linkuse as main transcriptc.1820C>T p.Pro607Leu missense_variant 15/22 ENST00000394773.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EML3ENST00000394773.7 linkuse as main transcriptc.1820C>T p.Pro607Leu missense_variant 15/221 NM_153265.3 P4Q32P44-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 13, 2024The c.1820C>T (p.P607L) alteration is located in exon 15 (coding exon 15) of the EML3 gene. This alteration results from a C to T substitution at nucleotide position 1820, causing the proline (P) at amino acid position 607 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
0.86
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.28
T;.;T;T;.
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D
MetaSVM
Uncertain
0.57
D
MutationAssessor
Pathogenic
3.8
H;.;.;.;H
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-9.0
D;D;D;D;D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.78
MutPred
0.80
.;Gain of stability (P = 0.2008);.;.;.;
MVP
0.92
MPC
1.8
ClinPred
1.0
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.95
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765218426; hg19: chr11-62373208; API