1-201997524-G-T

Variant names:

• chr1-201997524-G-T
• rs200764787
• NM_020216.4:c.1060G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020216.4(RNPEP):​c.1060G>T​(p.Ala354Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A354T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ELF3-AS1 (HGNC:40211): (ELF3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.1060G>T	p.Ala354Ser	missense_variant	Exon 5 of 11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319182.2	c.667G>T	p.Ala223Ser	missense_variant	Exon 5 of 11		NP_001306111.1
RNPEP	NM_001319183.2	c.190G>T	p.Ala64Ser	missense_variant	Exon 4 of 10		NP_001306112.1
RNPEP	NM_001319184.2	c.190G>T	p.Ala64Ser	missense_variant	Exon 4 of 10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.1060G>T	p.Ala354Ser	missense_variant	Exon 5 of 11	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461732 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.18	T;T;T;D
Sift4G	Benign	0.072	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.72
MutPred		0.69		Loss of helix (P = 0.2271);.;.;.;
MVP		0.49
MPC		0.59
ClinPred		0.88	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs200764787; hg19: chr1-201966652;