1-51878485-G-C

Variant names:

• chr1-51878485-G-C
• NM_001101662.2:c.131C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001101662.2(NRDC):​c.131C>G​(p.Pro44Arg) 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. 14/21 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. P44L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRDC NM_001101662.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

Genes affected

NRDC (HGNC:7995): (nardilysin convertase) This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066711575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2	c.131C>G	p.Pro44Arg	missense_variant	Exon 1 of 31	ENST00000352171.12	NP_001095132.1
NRDC	NM_002525.3	c.131C>G	p.Pro44Arg	missense_variant	Exon 1 of 33		NP_002516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRDC	ENST00000352171.12	c.131C>G	p.Pro44Arg	missense_variant	Exon 1 of 31	1	NM_001101662.2	ENSP00000262679.8
NRDC	ENST00000354831.11	c.131C>G	p.Pro44Arg	missense_variant	Exon 1 of 33	1		ENSP00000346890.7
NRDC	ENST00000468722.1	n.239C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3
NRDC	ENST00000491410.1	n.287C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.47	N;N;.
REVEL	Benign	0.020
Sift	Benign	0.31	T;T;.
Sift4G	Benign	0.19	T;T;T
Polyphen		0.62	P;.;.
Vest4		0.14
MutPred		0.42		Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);
MVP		0.043
MPC		0.10
ClinPred		0.61	D
GERP RS		3.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.042
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-52344157;