chr3-128176383-A-G

Variant names:

• chr3-128176383-A-G
• rs2687729
• NM_021937.5:c.316+22560A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021937.5(EEFSEC):​c.316+22560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,696 control chromosomes in the GnomAD database, including 6,737 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 (6737 hom., cov: 30)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 45 publications found

Genes affected

EEFSEC (HGNC:24614): (eukaryotic elongation factor, selenocysteine-tRNA specific) Predicted to enable translation elongation factor activity. Predicted to be involved in selenocysteine incorporation. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

EEFSEC Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with progressive spasticity and brain abnormalities

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.316+22560A>G		intron_variant	Intron 1 of 6	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.316+22560A>G		intron_variant	Intron 1 of 6	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.316+22560A>G		intron_variant	Intron 1 of 4	5		ENSP00000417660.1
EEFSEC	ENST00000484438.1	n.156+22560A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44437 AN: 151578 Hom.: 6730 Cov.: 30

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44463 AN: 151696 Hom.: 6737 Cov.: 30 AF XY: 0.295 AC XY: 21862 AN XY: 74106

African (AFR) AF: 0.343 AC: 14160 AN: 41312

American (AMR) AF: 0.309 AC: 4715 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5164

South Asian (SAS) AF: 0.370 AC: 1772 AN: 4792

European-Finnish (FIN) AF: 0.279 AC: 2918 AN: 10454

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18340 AN: 67948

Other (OTH) AF: 0.266 AC: 560 AN: 2104

Alfa AF: 0.271 Hom.: 19529

Bravo AF: 0.289

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs2687729; hg19: chr3-127895226;