NM_203414.3:c.187C>T

Variant names:

• chr17-7252997-C-T
• rs763642573
• NM_203414.3:c.187C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_203414.3(ELP5):​c.187C>T​(p.Arg63Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ELP5 NM_203414.3 missense, splice_region
• Scores: Splicing: ADA: 0.01817
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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:):

CTDNEP1 (HGNC:19085): (CTD nuclear envelope phosphatase 1) Enables protein serine/threonine phosphatase activity. Involved in several processes, including positive regulation of triglyceride biosynthetic process; protein dephosphorylation; and protein localization to nucleus. Located in endoplasmic reticulum membrane; lipid droplet; and nuclear membrane. Part of Nem1-Spo7 phosphatase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

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.187C>T	p.Arg63Trp	missense splice_region	Exon 3 of 8	NP_981959.2	Q8TE02-5
	ELP5	NM_015362.5		c.187C>T	p.Arg63Trp	missense splice_region	Exon 4 of 9	NP_056177.4
	ELP5	NM_203415.4		c.187C>T	p.Arg63Trp	missense splice_region	Exon 4 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.187C>T	p.Arg63Trp	missense splice_region	Exon 3 of 8	ENSP00000379869.3	Q8TE02-5
	ELP5	ENST00000396627.7	TSL:1	c.187C>T	p.Arg63Trp	missense splice_region	Exon 4 of 9	ENSP00000379868.3	Q8TE02-5
	ELP5	ENST00000574993.6	TSL:1	c.187C>T	p.Arg63Trp	missense splice_region	Exon 3 of 6	ENSP00000459835.2	Q8TE02-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251478 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461676 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111828

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.14
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.86		Loss of disorder (P = 0.0532)
MVP		0.72
MPC		0.64
ClinPred		0.97	D
GERP RS		2.6
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.45
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.018
dbscSNV1_RF	Benign	0.16
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: rs763642573; hg19: chr17-7156316;