17-7258637-G-A

Variant names:

• chr17-7258637-G-A
• rs78782818
• NM_203414.3:c.641G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_203414.3(ELP5):​c.641G>A​(p.Gly214Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,614,044 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (78 hom.)
• Consequence: ELP5 NM_203414.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0570
• Publications: 9 publications found

Genes affected

ELP5 (HGNC:30617): (elongator acetyltransferase complex subunit 5) Predicted to contribute to tRNA binding activity. Predicted to be involved in positive regulation of cell migration and tRNA modification. Located in cytosol and nucleoplasm. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262302 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002267003).
• BP6: Variant 17-7258637-G-A is Benign according to our data. Variant chr17-7258637-G-A is described in ClinVar as Benign. ClinVar VariationId is 783763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203414.3. 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
	ELP5	NM_203414.3	MANE Select	c.641G>A	p.Gly214Glu	missense	Exon 6 of 8	NP_981959.2	Q8TE02-5
	ELP5	NM_015362.5		c.641G>A	p.Gly214Glu	missense	Exon 7 of 9	NP_056177.4
	ELP5	NM_203415.4		c.641G>A	p.Gly214Glu	missense	Exon 7 of 9	NP_981960.2	Q8TE02-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP5	ENST00000396628.7	TSL:1 MANE Select	c.641G>A	p.Gly214Glu	missense	Exon 6 of 8	ENSP00000379869.3	Q8TE02-5
	ELP5	ENST00000396627.7	TSL:1	c.641G>A	p.Gly214Glu	missense	Exon 7 of 9	ENSP00000379868.3	Q8TE02-5
	ELP5	ENST00000574993.6	TSL:1	c.641G>A	p.Gly214Glu	missense	Exon 6 of 6	ENSP00000459835.2	Q8TE02-2

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2656 AN: 152036 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00513 AC: 1288 AN: 251278 AF XY: 0.00389

Gnomad AFR exome AF: 0.0674

Gnomad AMR exome AF: 0.00396

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00204 AC: 2989 AN: 1461890 Hom.: 78 Cov.: 30 AF XY: 0.00177 AC XY: 1285 AN XY: 727244

African (AFR) AF: 0.0671 AC: 2247 AN: 33478

American (AMR) AF: 0.00452 AC: 202 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.000218 AC: 242 AN: 1112012

Other (OTH) AF: 0.00424 AC: 256 AN: 60396

GnomAD4 genome AF: 0.0174 AC: 2655 AN: 152154 Hom.: 97 Cov.: 32 AF XY: 0.0166 AC XY: 1232 AN XY: 74386

African (AFR) AF: 0.0600 AC: 2488 AN: 41488

American (AMR) AF: 0.00766 AC: 117 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68006

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00679 Hom.: 60

Bravo AF: 0.0208

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0570 AC: 251

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00600 AC: 729

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.3
DANN	Benign	0.69
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.057
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.025
Sift	Benign	0.69	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.12
MVP		0.21
MPC		0.20
ClinPred		0.00074	T
GERP RS		-0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.031
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78782818; hg19: chr17-7161956;