3-128262143-G-A

Variant names:

• chr3-128262143-G-A
• rs116353475
• NM_021937.5:c.540G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021937.5(EEFSEC):​c.540G>A​(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,614,084 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (39 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (53 hom.)
• Consequence: EEFSEC NM_021937.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.99
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-128262143-G-A is Benign according to our data. Variant chr3-128262143-G-A is described in ClinVar as Benign. ClinVar VariationId is 775907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.99 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0146 (2227/152242) while in subpopulation AFR AF = 0.0507 (2106/41520). AF 95% confidence interval is 0.0489. There are 39 homozygotes in GnomAd4. There are 1051 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	NM_021937.5	MANE Select	c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 7	NP_068756.2	P57772-1
	EEFSEC	NM_001437809.1		c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 8	NP_001424738.1
	EEFSEC	NM_001437810.1		c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 7	NP_001424739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	ENST00000254730.11	TSL:1 MANE Select	c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 7	ENSP00000254730.5	P57772-1
	EEFSEC	ENST00000868107.1		c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 8	ENSP00000538166.1
	EEFSEC	ENST00000868109.1		c.540G>A	p.Pro180Pro	synonymous	Exon 3 of 8	ENSP00000538168.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2223 AN: 152126 Hom.: 39 Cov.: 31

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00385 AC: 969 AN: 251448 AF XY: 0.00286

Gnomad AFR exome AF: 0.0502

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00158 AC: 2312 AN: 1461842 Hom.: 53 Cov.: 30 AF XY: 0.00139 AC XY: 1009 AN XY: 727214

African (AFR) AF: 0.0514 AC: 1719 AN: 33472

American (AMR) AF: 0.00360 AC: 161 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000155 AC: 172 AN: 1111990

Other (OTH) AF: 0.00363 AC: 219 AN: 60392

GnomAD4 genome AF: 0.0146 AC: 2227 AN: 152242 Hom.: 39 Cov.: 31 AF XY: 0.0141 AC XY: 1051 AN XY: 74432

African (AFR) AF: 0.0507 AC: 2106 AN: 41520

American (AMR) AF: 0.00555 AC: 85 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68018

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00668 Hom.: 6

Bravo AF: 0.0169

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.46
PhyloP100		-4.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116353475; hg19: chr3-127980986; COSMIC: COSV54633100;