chr8-143580164-G-T

Variant names:

• chr8-143580164-G-T
• rs780189803
• NM_001130053.5:c.1753C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001130053.5(EEF1D):​c.1753C>A​(p.Arg585Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R585C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EEF1D NM_001130053.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 4 publications found

Genes affected

EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

ENSG00000279605 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: REVEL computational evidence supports a deleterious effect, 0.909

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130053.5. 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
	EEF1D	NM_001130053.5	MANE Select	c.1753C>A	p.Arg585Ser	missense	Exon 9 of 10	NP_001123525.3	P29692-2
	EEF1D	NM_032378.7		c.1753C>A	p.Arg585Ser	missense	Exon 9 of 10	NP_115754.4
	EEF1D	NM_001130055.4		c.655C>A	p.Arg219Ser	missense	Exon 8 of 9	NP_001123527.1	P29692-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1D	ENST00000618139.4	TSL:5 MANE Select	c.1753C>A	p.Arg585Ser	missense	Exon 9 of 10	ENSP00000484536.2	P29692-2
	EEF1D	ENST00000532741.5	TSL:1	c.1903C>A	p.Arg635Ser	missense	Exon 7 of 8	ENSP00000434070.1	E9PRY8
	EEF1D	ENST00000442189.6	TSL:1	c.1753C>A	p.Arg585Ser	missense	Exon 9 of 10	ENSP00000391944.2	P29692-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		5.6
Vest4		0.17
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
Mutation Taster		=40/160	disease causing (fs/PTC)

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: rs780189803; hg19: chr8-144662334;