rs369674762

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-143580550-G-C
• chr8-143580550-G-A
• chr8-143580550-G-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>G​(p.Pro556Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: EEF1D NM_001130053.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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, 0.783

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>G	p.Pro556Ala	missense	Exon 8 of 10	NP_001123525.3	P29692-2
	EEF1D	NM_032378.7		c.1666C>G	p.Pro556Ala	missense	Exon 8 of 10	NP_115754.4
	EEF1D	NM_001130055.4		c.568C>G	p.Pro190Ala	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>G	p.Pro556Ala	missense	Exon 8 of 10	ENSP00000484536.2	P29692-2
	EEF1D	ENST00000532741.5	TSL:1	c.1816C>G	p.Pro606Ala	missense	Exon 6 of 8	ENSP00000434070.1	E9PRY8
	EEF1D	ENST00000442189.6	TSL:1	c.1666C>G	p.Pro556Ala	missense	Exon 8 of 10	ENSP00000391944.2	P29692-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250942 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000616

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460770 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726708

African (AFR) AF: 0.000149 AC: 5 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: 0.0000116 AC: 1 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: 0.00000270 AC: 3 AN: 1111828

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.0053	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.9
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.39
Sift	Benign	0.033	D
Sift4G	Uncertain	0.053	T
Polyphen		0.37	B
Vest4		0.49
MVP		0.85
MPC		0.14
ClinPred		0.98	D
GERP RS		4.6
PromoterAI		0.023	Neutral
Varity_R		0.56
gMVP		0.33
Mutation Taster		=33/67	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;