NM_001001414.2:c.185C>G

Variant names:

• chr19-39197167-C-G
• rs889943123
• NM_001001414.2:c.185C>G

Variant summary

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

The NM_001001414.2(NCCRP1):​c.185C>G​(p.Ala62Gly) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A62V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCCRP1 NM_001001414.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 0 publications found

Genes affected

NCCRP1 (HGNC:33739): (NCCRP1, F-box associated domain containing) Predicted to contribute to ubiquitin protein ligase activity. Involved in positive regulation of cell population proliferation. Located in cytoplasm. [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=0.033507258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001414.2. 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
	NCCRP1	NM_001001414.2	MANE Select	c.185C>G	p.Ala62Gly	missense	Exon 1 of 6	NP_001001414.1	Q6ZVX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCCRP1	ENST00000339852.5	TSL:1 MANE Select	c.185C>G	p.Ala62Gly	missense	Exon 1 of 6	ENSP00000342137.3	Q6ZVX7
	NCCRP1	ENST00000855675.1		c.185C>G	p.Ala62Gly	missense	Exon 1 of 6	ENSP00000525734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.94
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.58
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Benign	0.13	T
Sift4G	Benign	0.34	T
Polyphen		0.0030	B
Vest4		0.069
MutPred		0.12		Gain of catalytic residue at A62 (P = 0.0848)
MVP		0.040
MPC		1.3
ClinPred		0.072	T
GERP RS		-0.44
PromoterAI		-0.020	Neutral
Varity_R		0.038
gMVP		0.13
Mutation Taster		=100/0	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: rs889943123; hg19: chr19-39687807;