chr11-62611329-T-C

Variant names:

• chr11-62611329-T-C
• rs11553576
• NM_153265.3:c.210A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001300793.2(EML3):​c.213A>G​(p.Pro71Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,612,638 control chromosomes in the GnomAD database, including 96,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6979 hom., cov: 32)
  • Exomes 𝑓: 0.34 (89331 hom.)
• Consequence: EML3 NM_001300793.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 28 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.049).
• BP7: Synonymous conserved (PhyloP=-0.983 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300793.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	NM_153265.3	MANE Select	c.210A>G	p.Pro70Pro	synonymous	Exon 3 of 22	NP_694997.2
	EML3	NM_001300793.2		c.213A>G	p.Pro71Pro	synonymous	Exon 3 of 22	NP_001287722.1
	EML3	NM_001300794.2		c.210A>G	p.Pro70Pro	synonymous	Exon 3 of 22	NP_001287723.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	ENST00000394773.7	TSL:1 MANE Select	c.210A>G	p.Pro70Pro	synonymous	Exon 3 of 22	ENSP00000378254.2
	EML3	ENST00000964792.1		c.372A>G	p.Pro124Pro	synonymous	Exon 4 of 23	ENSP00000634851.1
	EML3	ENST00000529309.5	TSL:2	c.210A>G	p.Pro70Pro	synonymous	Exon 3 of 22	ENSP00000434513.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44380 AN: 151974 Hom.: 6969 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.283 AC: 69399 AN: 245480 AF XY: 0.290

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.365

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.342 AC: 500191 AN: 1460546 Hom.: 89331 Cov.: 63 AF XY: 0.341 AC XY: 247651 AN XY: 726586

African (AFR) AF: 0.226 AC: 7563 AN: 33464

American (AMR) AF: 0.164 AC: 7314 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10954 AN: 26078

East Asian (EAS) AF: 0.138 AC: 5469 AN: 39696

South Asian (SAS) AF: 0.252 AC: 21706 AN: 86234

European-Finnish (FIN) AF: 0.246 AC: 12933 AN: 52544

Middle Eastern (MID) AF: 0.344 AC: 1976 AN: 5752

European-Non Finnish (NFE) AF: 0.371 AC: 412684 AN: 1111772

Other (OTH) AF: 0.325 AC: 19592 AN: 60366

GnomAD4 genome AF: 0.292 AC: 44421 AN: 152092 Hom.: 6979 Cov.: 32 AF XY: 0.285 AC XY: 21161 AN XY: 74348

African (AFR) AF: 0.229 AC: 9484 AN: 41494

American (AMR) AF: 0.239 AC: 3655 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1448 AN: 3466

East Asian (EAS) AF: 0.0997 AC: 515 AN: 5166

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4820

European-Finnish (FIN) AF: 0.227 AC: 2405 AN: 10586

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24734 AN: 67960

Other (OTH) AF: 0.324 AC: 681 AN: 2104

Alfa AF: 0.340 Hom.: 14774

Bravo AF: 0.288

Asia WGS AF: 0.166 AC: 581 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.3
DANN	Benign	0.61
PhyloP100		-0.98
PromoterAI		-0.0092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11553576; hg19: chr11-62378801; COSMIC: COSV53882850; COSMIC: COSV53882850;