rs768714658

Variant names:

• chr11-62602481-G-T
• rs768714658
• NM_153265.3:c.2685C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-62602481-G-T
• chr11-62602481-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153265.3(EML3):​c.2685C>A​(p.Asp895Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,536,534 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.786
• 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032463133).

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.2685C>A	p.Asp895Glu	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.2578C>A	p.Arg860Ser	missense	Exon 22 of 22	NP_001287722.1
	EML3	NM_001300794.2		c.2575C>A	p.Arg859Ser	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.2685C>A	p.Asp895Glu	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
	EML3	ENST00000964792.1		c.2796C>A	p.Asp932Glu	missense	Exon 23 of 23	ENSP00000634851.1
	EML3	ENST00000529309.5	TSL:2	c.2575C>A	p.Arg859Ser	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152180 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.0000797 AC: 11 AN: 138056 AF XY: 0.0000536

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 52 AN: 1384354 Hom.: 0 Cov.: 39 AF XY: 0.0000337 AC XY: 23 AN XY: 681924

African (AFR) AF: 0.00117 AC: 36 AN: 30776

American (AMR) AF: 0.000118 AC: 4 AN: 33786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24424

East Asian (EAS) AF: 0.00 AC: 0 AN: 35302

South Asian (SAS) AF: 0.00 AC: 0 AN: 78274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071260

Other (OTH) AF: 0.000209 AC: 12 AN: 57290

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152180 Hom.: 1 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74336

African (AFR) AF: 0.00106 AC: 44 AN: 41454

American (AMR) AF: 0.000458 AC: 7 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.000438

ExAC AF: 0.0000273 AC: 2

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	Benign	0.15
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.79
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.075
Sift	Benign	0.70	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.80	P
Vest4		0.068
MutPred		0.14		Gain of glycosylation at P891 (P = 0.1298)
MVP		0.27
MPC		0.65
ClinPred		0.025	T
GERP RS		0.77
Varity_R		0.046
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs768714658; hg19: chr11-62369953; COSMIC: COSV107226439; COSMIC: COSV107226439;