3-128305133-G-A

Variant names:

• chr3-128305133-G-A
• rs2811392
• NM_021937.5:c.787-36100G>A

Variant summary

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

The NM_021937.5(EEFSEC):​c.787-36100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,076 control chromosomes in the GnomAD database, including 56,045 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 0.86 (56045 hom., cov: 33)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 6 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.787-36100G>A		intron_variant	Intron 4 of 6	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.787-36100G>A		intron_variant	Intron 4 of 6	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.622-36100G>A		intron_variant	Intron 3 of 4	5		ENSP00000417660.1
EEFSEC	ENST00000484438.1	n.365-36100G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130169 AN: 151958 Hom.: 55988 Cov.: 33

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.857 AC: 130285 AN: 152076 Hom.: 56045 Cov.: 33 AF XY: 0.858 AC XY: 63816 AN XY: 74348

African (AFR) AF: 0.771 AC: 31969 AN: 41442

American (AMR) AF: 0.896 AC: 13710 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3123 AN: 3468

East Asian (EAS) AF: 0.995 AC: 5160 AN: 5188

South Asian (SAS) AF: 0.836 AC: 4043 AN: 4834

European-Finnish (FIN) AF: 0.891 AC: 9405 AN: 10554

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60028 AN: 67974

Other (OTH) AF: 0.869 AC: 1834 AN: 2110

Alfa AF: 0.858 Hom.: 7268

Bravo AF: 0.856

Asia WGS AF: 0.916 AC: 3177 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.56
PhyloP100		0.14
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: rs2811392; hg19: chr3-128023976; COSMIC: COSV54623179;