chr3-128153651-G-T

Variant names:

• chr3-128153651-G-T
• rs148745324
• NM_021937.5:c.144G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_021937.5(EEFSEC):​c.144G>T​(p.Thr48Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,598,438 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0038 (20 hom.)
• Consequence: EEFSEC NM_021937.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.845

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]

RUVBL1 (HGNC:10474): (RuvB like AAA ATPase 1) This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-128153651-G-T is Benign according to our data. Variant chr3-128153651-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.845 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.144G>T	p.Thr48Thr	synonymous_variant	Exon 1 of 7	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.144G>T	p.Thr48Thr	synonymous_variant	Exon 1 of 7	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.144G>T	p.Thr48Thr	synonymous_variant	Exon 1 of 5	5		ENSP00000417660.1
RUVBL1	ENST00000464873.5	c.-488C>A		5_prime_UTR_variant	Exon 1 of 10	2		ENSP00000420738.1
EEFSEC	ENST00000484438.1	n.-17G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152142 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00253 AC: 561 AN: 221714 AF XY: 0.00265

Gnomad AFR exome AF: 0.000792

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00622

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00318

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00382 AC: 5527 AN: 1446188 Hom.: 20 Cov.: 31 AF XY: 0.00384 AC XY: 2766 AN XY: 719776

Gnomad4 AFR exome AF: 0.000896 AC: 29 AN: 32356

Gnomad4 AMR exome AF: 0.00110 AC: 49 AN: 44510

Gnomad4 ASJ exome AF: 0.00762 AC: 198 AN: 25988

Gnomad4 EAS exome AF: 0.0000254 AC: 1 AN: 39314

Gnomad4 SAS exome AF: 0.00373 AC: 319 AN: 85518

Gnomad4 FIN exome AF: 0.000468 AC: 20 AN: 42738

Gnomad4 NFE exome AF: 0.00428 AC: 4757 AN: 1110184

Gnomad4 Remaining exome AF: 0.00245 AC: 147 AN: 60040

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152250 Hom.: 1 Cov.: 29 AF XY: 0.00230 AC XY: 171 AN XY: 74428

Gnomad4 AFR AF: 0.000818 AC: 0.000817976 AN: 0.000817976

Gnomad4 AMR AF: 0.000915 AC: 0.000914674 AN: 0.000914674

Gnomad4 ASJ AF: 0.00692 AC: 0.00691643 AN: 0.00691643

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00166 AC: 0.00165769 AN: 0.00165769

Gnomad4 FIN AF: 0.000753 AC: 0.000753154 AN: 0.000753154

Gnomad4 NFE AF: 0.00402 AC: 0.0040153 AN: 0.0040153

Gnomad4 OTH AF: 0.000945 AC: 0.00094518 AN: 0.00094518

Alfa AF: 0.00296 Hom.: 1

Bravo AF: 0.00228

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EEFSEC: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=287/13	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs148745324; hg19: chr3-127872494;