rs11553576

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153265.3(EML3):​c.210A>G​(p.Pro70Pro) 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_153265.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML3	NM_153265.3	c.210A>G	p.Pro70Pro	synonymous_variant	Exon 3 of 22	ENST00000394773.7	NP_694997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML3	ENST00000394773.7	c.210A>G	p.Pro70Pro	synonymous_variant	Exon 3 of 22	1	NM_153265.3	ENSP00000378254.2

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

GnomAD3 exomes AF: 0.283 AC: 69399 AN: 245480 Hom.: 10976 AF XY: 0.290 AC XY: 38850 AN XY: 133738

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 SAS exome AF: 0.249

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

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.325

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.324

Alfa AF: 0.353 Hom.: 12065

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.3
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs11553576; hg19: chr11-62378801; COSMIC: COSV53882850; COSMIC: COSV53882850;