8-143580550-G-T

Variant names:

• chr8-143580550-G-T
• rs369674762
• NM_001130053.5:c.1666C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130053.5(EEF1D):​c.1666C>A​(p.Pro556Thr) 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 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. P556A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: EEF1D NM_001130053.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 2 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]

ENSG00000254741 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

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.1666C>A	p.Pro556Thr	missense	Exon 8 of 10	NP_001123525.3	P29692-2
	EEF1D	NM_032378.7		c.1666C>A	p.Pro556Thr	missense	Exon 8 of 10	NP_115754.4
	EEF1D	NM_001130055.4		c.568C>A	p.Pro190Thr	missense	Exon 7 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.1666C>A	p.Pro556Thr	missense	Exon 8 of 10	ENSP00000484536.2	P29692-2
	EEF1D	ENST00000532741.5	TSL:1	c.1816C>A	p.Pro606Thr	missense	Exon 6 of 8	ENSP00000434070.1	E9PRY8
	EEF1D	ENST00000442189.6	TSL:1	c.1666C>A	p.Pro556Thr	missense	Exon 8 of 10	ENSP00000391944.2	P29692-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250942 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.46
Sift	Benign	0.032	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.72
MutPred		0.29		Gain of phosphorylation at P606 (P = 0.032)
MVP		0.86
MPC		0.25
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		0.0013	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.56
gMVP		0.45
Mutation Taster		=37/63	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: rs369674762; hg19: chr8-144662720;