11-62602660-C-G

Variant names:

• chr11-62602660-C-G
• rs749272847
• NM_153265.3:c.2506G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153265.3(EML3):​c.2506G>C​(p.Gly836Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,444,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25872818).

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.2506G>C	p.Gly836Arg	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.2399G>C	p.Arg800Pro	missense	Exon 22 of 22	NP_001287722.1
	EML3	NM_001300794.2		c.2396G>C	p.Arg799Pro	missense	Exon 22 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.2506G>C	p.Gly836Arg	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
	EML3	ENST00000964792.1		c.2617G>C	p.Gly873Arg	missense	Exon 23 of 23	ENSP00000634851.1
	EML3	ENST00000529309.5	TSL:2	c.2396G>C	p.Arg799Pro	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1444442 Hom.: 0 Cov.: 38 AF XY: 0.00000418 AC XY: 3 AN XY: 717888

African (AFR) AF: 0.00 AC: 0 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 43612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39028

South Asian (SAS) AF: 0.00 AC: 0 AN: 84724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1106706

Other (OTH) AF: 0.00 AC: 0 AN: 59726

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T
Eigen	Benign	0.073
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PhyloP100		1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.076
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.53	T
Polyphen		0.66	P
Vest4		0.12
MutPred		0.35		Gain of MoRF binding (P = 0.0075)
MVP		0.49
MPC		1.5
ClinPred		0.76	D
GERP RS		4.0
Varity_R		0.16
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs749272847; hg19: chr11-62370132;