11-62602665-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153265.3(EML3):​c.2501T>A​(p.Met834Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059341878).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EML3NM_153265.3 linkc.2501T>A p.Met834Lys missense_variant Exon 22 of 22 ENST00000394773.7 NP_694997.2 Q32P44-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EML3ENST00000394773.7 linkc.2501T>A p.Met834Lys missense_variant Exon 22 of 22 1 NM_153265.3 ENSP00000378254.2 Q32P44-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000932
AC:
2
AN:
214640
Hom.:
0
AF XY:
0.0000169
AC XY:
2
AN XY:
118542
show subpopulations
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:
0.0000212
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000346
AC:
5
AN:
1444816
Hom.:
0
Cov.:
39
AF XY:
0.00000418
AC XY:
3
AN XY:
718068
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000452
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000846
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
20
DANN
Benign
0.93
DEOGEN2
Benign
0.0066
T;.
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.35
T;T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-0.95
T
PROVEAN
Benign
0.31
N;N
REVEL
Benign
0.096
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.48
T;T
Polyphen
0.0010
B;B
Vest4
0.082
MutPred
0.30
Loss of sheet (P = 0.1158);.;
MVP
0.12
ClinPred
0.14
T
GERP RS
3.8
gMVP
0.70

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

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

Other links and lift over

dbSNP: rs774505119; hg19: chr11-62370137; API