1-51800680-G-A

Variant names:

• chr1-51800680-G-A
• NM_001101662.2:c.2317C>T
• NRDC p.Leu773Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101662.2(NRDC):​c.2317C>T​(p.Leu773Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L773L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.233).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101662.2. 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
	NRDC	NM_001101662.2	MANE Select	c.2317C>T	p.Leu773Leu	synonymous	Exon 21 of 31	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.2521C>T	p.Leu841Leu	synonymous	Exon 23 of 33	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.2125C>T	p.Leu709Leu	synonymous	Exon 23 of 33	NP_001229290.1	G3V1R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	ENST00000352171.12	TSL:1 MANE Select	c.2317C>T	p.Leu773Leu	synonymous	Exon 21 of 31	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.2521C>T	p.Leu841Leu	synonymous	Exon 23 of 33	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.2125C>T	p.Leu709Leu	synonymous	Exon 23 of 33	ENSP00000444416.1	G3V1R5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-52266352;