3-128376809-T-C

Variant names:

• chr3-128376809-T-C
• rs3021461
• NM_021937.5:c.1600+18436T>C

Variant summary

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

The NM_021937.5(EEFSEC):​c.1600+18436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,016 control chromosomes in the GnomAD database, including 7,034 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 0.30 (7034 hom., cov: 32)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.1600+18436T>C		intron_variant	Intron 6 of 6	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.1600+18436T>C		intron_variant	Intron 6 of 6	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.1279-31260T>C		intron_variant	Intron 4 of 4	5		ENSP00000417660.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44798 AN: 151898 Hom.: 7018 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.295 AC: 44850 AN: 152016 Hom.: 7034 Cov.: 32 AF XY: 0.299 AC XY: 22178 AN XY: 74290

African (AFR) AF: 0.368 AC: 15271 AN: 41450

American (AMR) AF: 0.344 AC: 5255 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2464 AN: 5136

South Asian (SAS) AF: 0.368 AC: 1770 AN: 4806

European-Finnish (FIN) AF: 0.255 AC: 2693 AN: 10562

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15582 AN: 67994

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.248 Hom.: 8875

Bravo AF: 0.302

Asia WGS AF: 0.384 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.63
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: rs3021461; hg19: chr3-128095652;