17-7256992-C-G

Variant names:

• chr17-7256992-C-G
• rs769734868
• NM_203414.3:c.545C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203414.3(ELP5):​c.545C>G​(p.Ser182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. S182L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELP5 NM_203414.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28862393).

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.545C>G	p.Ser182Trp	missense	Exon 5 of 8	NP_981959.2	Q8TE02-5
	ELP5	NM_015362.5		c.545C>G	p.Ser182Trp	missense	Exon 6 of 9	NP_056177.4
	ELP5	NM_203415.4		c.545C>G	p.Ser182Trp	missense	Exon 6 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.545C>G	p.Ser182Trp	missense	Exon 5 of 8	ENSP00000379869.3	Q8TE02-5
	ELP5	ENST00000396627.7	TSL:1	c.545C>G	p.Ser182Trp	missense	Exon 6 of 9	ENSP00000379868.3	Q8TE02-5
	ELP5	ENST00000574993.6	TSL:1	c.545C>G	p.Ser182Trp	missense	Exon 5 of 6	ENSP00000459835.2	Q8TE02-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247056 AF XY: 0.00000747

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457712 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725190

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110978

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.32
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.23
Sift	Benign	0.056	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.015	B
Vest4		0.64
MutPred		0.63		Loss of disorder (P = 0.0076)
MVP		0.48
MPC		0.71
ClinPred		0.81	D
GERP RS		3.2
Varity_R		0.10
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs769734868; hg19: chr17-7160311;