chr3-128200203-G-T

Variant names:

• chr3-128200203-G-T
• rs2811485
• NM_021937.5:c.316+46380G>T

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+46380G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,730 control chromosomes in the GnomAD database, including 16,198 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 0.42 (16198 hom., cov: 33)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 7 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

ENSG00000303801 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.316+46380G>T		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+46380G>T		intron_variant	Intron 1 of 6	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.316+46380G>T		intron_variant	Intron 1 of 4	5		ENSP00000417660.1
EEFSEC	ENST00000484438.1	n.156+46380G>T		intron_variant	Intron 1 of 2	3
ENSG00000303801	ENST00000797268.1	n.294+5542G>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64038 AN: 151612 Hom.: 16166 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.423 AC: 64129 AN: 151730 Hom.: 16198 Cov.: 33 AF XY: 0.423 AC XY: 31358 AN XY: 74154

African (AFR) AF: 0.711 AC: 29329 AN: 41258

American (AMR) AF: 0.424 AC: 6467 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2394 AN: 5148

South Asian (SAS) AF: 0.426 AC: 2054 AN: 4826

European-Finnish (FIN) AF: 0.291 AC: 3071 AN: 10548

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18505 AN: 67916

Other (OTH) AF: 0.380 AC: 802 AN: 2108

Alfa AF: 0.305 Hom.: 3410

Bravo AF: 0.441

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.19
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: rs2811485; hg19: chr3-127919046;