18-24430347-C-A

Variant names:

• chr18-24430347-C-A
• rs759107422
• NM_018439.4:c.244C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018439.4(IMPACT):​c.244C>A​(p.Arg82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R82C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IMPACT NM_018439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.244C>A	p.Arg82Ser	missense	Exon 4 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.244C>A	p.Arg82Ser	missense	Exon 4 of 11	ENSP00000284202.4	Q9P2X3-1
	IMPACT	ENST00000580706.1	TSL:1	n.1480C>A		non_coding_transcript_exon	Exon 3 of 10
	IMPACT	ENST00000648078.1		c.244C>A	p.Arg82Ser	missense	Exon 4 of 12	ENSP00000497783.1	A0A3B3ITH3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444762 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 718988

African (AFR) AF: 0.00 AC: 0 AN: 32748

American (AMR) AF: 0.00 AC: 0 AN: 40344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 39122

South Asian (SAS) AF: 0.00 AC: 0 AN: 82602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106070

Other (OTH) AF: 0.00 AC: 0 AN: 59556

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.17
Sift	Benign	0.050	D
Sift4G	Benign	0.26	T
Polyphen		0.46	P
Vest4		0.65
MutPred		0.62		Gain of disorder (P = 0.0435)
MVP		0.46
MPC		0.15
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.50
gMVP		0.65
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs759107422; hg19: chr18-22010311;