11-62604020-C-A

Variant names:

• chr11-62604020-C-A
• NM_153265.3:c.2093G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_153265.3(EML3):​c.2093G>T​(p.Gly698Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G698C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153265.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	NM_153265.3	MANE Select	c.2093G>T	p.Gly698Val	missense	Exon 18 of 22	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.2096G>T	p.Gly699Val	missense	Exon 18 of 22	NP_001287722.1
	EML3	NM_001300794.2		c.2093G>T	p.Gly698Val	missense	Exon 18 of 22	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	ENST00000394773.7	TSL:1 MANE Select	c.2093G>T	p.Gly698Val	missense	Exon 18 of 22	ENSP00000378254.2	Q32P44-1
	EML3	ENST00000964792.1		c.2204G>T	p.Gly735Val	missense	Exon 19 of 23	ENSP00000634851.1
	EML3	ENST00000529309.5	TSL:2	c.2093G>T	p.Gly698Val	missense	Exon 18 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.77		Gain of catalytic residue at G699 (P = 0.0312)
MVP		0.84
MPC		2.0
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.81
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr11-62371492;