11-62606109-C-T

Position:

• chr11-62606109-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153265.3(EML3):​c.1610G>A​(p.Arg537Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37046412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML3	NM_153265.3	c.1610G>A	p.Arg537Gln	missense_variant	13/22	ENST00000394773.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML3	ENST00000394773.7	c.1610G>A	p.Arg537Gln	missense_variant	13/22	1	NM_153265.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727122

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: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 04, 2024

The c.1610G>A (p.R537Q) alteration is located in exon 13 (coding exon 13) of the EML3 gene. This alteration results from a G to A substitution at nucleotide position 1610, causing the arginine (R) at amino acid position 537 to be replaced by a glutamine (Q). 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	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.041	T;.;T;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M;.;.;.;M
MutationTaster	Benign	0.97	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.048	D;D;T;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		0.99	D;D;B;D;D
Vest4		0.56
MutPred		0.48		.;Loss of MoRF binding (P = 0.0196);.;.;.;
MVP		0.36
MPC		1.7
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr11-62373581; COSMIC: COSV99604386; COSMIC: COSV99604386;