chr3-128319530-C-A

Variant names:

• chr3-128319530-C-A
• rs10934853
• NM_021937.5:c.787-21703C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021937.5(EEFSEC):​c.787-21703C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,060 control chromosomes in the GnomAD database, including 16,404 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 0.43 (16404 hom., cov: 33)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09
• Publications: 118 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021937.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	NM_021937.5	MANE Select	c.787-21703C>A		intron	N/A	NP_068756.2
	EEFSEC	NM_001437809.1		c.787-21456C>A		intron	N/A	NP_001424738.1
	EEFSEC	NM_001437810.1		c.787-21703C>A		intron	N/A	NP_001424739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	ENST00000254730.11	TSL:1 MANE Select	c.787-21703C>A		intron	N/A	ENSP00000254730.5
	EEFSEC	ENST00000483457.1	TSL:5	c.622-21703C>A		intron	N/A	ENSP00000417660.1
	EEFSEC	ENST00000484438.1	TSL:3	n.365-21703C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64650 AN: 151942 Hom.: 16380 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.426 AC: 64720 AN: 152060 Hom.: 16404 Cov.: 33 AF XY: 0.427 AC XY: 31731 AN XY: 74332

African (AFR) AF: 0.708 AC: 29366 AN: 41464

American (AMR) AF: 0.429 AC: 6556 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2430 AN: 5154

South Asian (SAS) AF: 0.456 AC: 2197 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3198 AN: 10582

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18769 AN: 67976

Other (OTH) AF: 0.382 AC: 805 AN: 2106

Alfa AF: 0.315 Hom.: 36499

Bravo AF: 0.441

Asia WGS AF: 0.451 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		3.1
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: rs10934853; hg19: chr3-128038373;