8-143580550-G-A

Variant names:

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

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>T​(p.Pro556Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EEF1D NM_001130053.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 0 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, 0.771

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>T	p.Pro556Ser	missense	Exon 8 of 10	NP_001123525.3	P29692-2
	EEF1D	NM_032378.7		c.1666C>T	p.Pro556Ser	missense	Exon 8 of 10	NP_115754.4
	EEF1D	NM_001130055.4		c.568C>T	p.Pro190Ser	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>T	p.Pro556Ser	missense	Exon 8 of 10	ENSP00000484536.2	P29692-2
	EEF1D	ENST00000532741.5	TSL:1	c.1816C>T	p.Pro606Ser	missense	Exon 6 of 8	ENSP00000434070.1	E9PRY8
	EEF1D	ENST00000442189.6	TSL:1	c.1666C>T	p.Pro556Ser	missense	Exon 8 of 10	ENSP00000391944.2	P29692-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460770 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111828

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		7.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.31		Gain of phosphorylation at P606 (P = 0.021)
MVP		0.87
MPC		0.36
ClinPred		1.0	D
GERP RS		4.6
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.64
gMVP		0.44
Mutation Taster		=32/68	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;