rs763279916

Variant names:

• chr3-128262219-A-C
• rs763279916
• NM_021937.5:c.616A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-128262219-A-C
• chr3-128262219-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021937.5(EEFSEC):​c.616A>C​(p.Ile206Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I206T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EEFSEC NM_021937.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.37
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27825582).

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.616A>C	p.Ile206Leu	missense	Exon 3 of 7	NP_068756.2	P57772-1
	EEFSEC	NM_001437809.1		c.616A>C	p.Ile206Leu	missense	Exon 3 of 8	NP_001424738.1
	EEFSEC	NM_001437810.1		c.616A>C	p.Ile206Leu	missense	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.616A>C	p.Ile206Leu	missense	Exon 3 of 7	ENSP00000254730.5	P57772-1
	EEFSEC	ENST00000868107.1		c.616A>C	p.Ile206Leu	missense	Exon 3 of 8	ENSP00000538166.1
	EEFSEC	ENST00000868109.1		c.616A>C	p.Ile206Leu	missense	Exon 3 of 8	ENSP00000538168.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251370 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000205 AC: 30 AN: 1461190 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726918

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111398

Other (OTH) AF: 0.0000331 AC: 2 AN: 60358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.51
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.082
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.010	N
PhyloP100		8.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.28
Sift	Benign	0.19	T
Sift4G	Benign	0.37	T
Polyphen		0.12	B
Vest4		0.58
MutPred		0.44		Gain of catalytic residue at I206 (P = 0.129)
MVP		0.47
MPC		0.11
ClinPred		0.36	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.42
Mutation Taster		=39/61	disease causing

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: rs763279916; hg19: chr3-127981062;