18-24440579-C-T

Variant names:

• chr18-24440579-C-T
• rs677688
• NM_018439.4:c.451C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018439.4(IMPACT):​c.451C>T​(p.Leu151Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IMPACT NM_018439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• Publications: 32 publications found

Genes affected

IMPACT (HGNC:20387): (impact RWD domain protein) Predicted to enable actin binding activity and ribosome binding activity. Predicted to be involved in several processes, including GCN2-mediated signaling; cellular response to starvation; and negative regulation of nitrogen compound metabolic process. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044926584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018439.4. 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
	IMPACT	NM_018439.4	MANE Select	c.451C>T	p.Leu151Phe	missense	Exon 6 of 11	NP_060909.2	Q9P2X3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPACT	ENST00000284202.9	TSL:1 MANE Select	c.451C>T	p.Leu151Phe	missense	Exon 6 of 11	ENSP00000284202.4	Q9P2X3-1
	IMPACT	ENST00000580706.1	TSL:1	n.1687C>T		non_coding_transcript_exon	Exon 5 of 10
	IMPACT	ENST00000648078.1		c.451C>T	p.Leu151Phe	missense	Exon 6 of 12	ENSP00000497783.1	A0A3B3ITH3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.6
DANN	Benign	0.90
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.70
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.015
Sift	Benign	0.72	T
Sift4G	Benign	0.74	T
Polyphen		0.0050	B
Vest4		0.067
MutPred		0.25		Gain of methylation at K152 (P = 0.0361)
MVP		0.067
MPC		0.067
ClinPred		0.022	T
GERP RS		2.4
Varity_R		0.019
gMVP		0.14
Mutation Taster		=97/3	polymorphism

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: rs677688; hg19: chr18-22020543;