chr11-62605156-G-A

Position:

• chr11-62605156-G-A

Variant summary

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

The NM_153265.3(EML3):​c.1939C>T​(p.His647Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 2.73

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML3	NM_153265.3	c.1939C>T	p.His647Tyr	missense_variant	16/22	ENST00000394773.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML3	ENST00000394773.7	c.1939C>T	p.His647Tyr	missense_variant	16/22	1	NM_153265.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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

May 13, 2024

The c.1939C>T (p.H647Y) alteration is located in exon 16 (coding exon 16) of the EML3 gene. This alteration results from a C to T substitution at nucleotide position 1939, causing the histidine (H) at amino acid position 647 to be replaced by a tyrosine (Y). 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	Benign	0.34
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;T;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.3	L;.;.;.;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D
REVEL	Benign	0.19
Sift	Benign	0.087	T;T;T;T;D
Sift4G	Uncertain	0.0030	D;D;T;D;D
Polyphen		0.94	P;D;B;D;D
Vest4		0.84
MutPred		0.64		.;Loss of sheet (P = 0.1501);.;.;.;
MVP		0.39
MPC		1.7
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1942450492; hg19: chr11-62372628;