19-39197013-G-A

Variant names:

• chr19-39197013-G-A
• rs1025745434
• NM_001001414.2:c.31G>A

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.31G>A​(p.Gly11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G11R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NCCRP1 NM_001001414.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• 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=0.05055189).

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.31G>A	p.Gly11Ser	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.31G>A	p.Gly11Ser	missense	Exon 1 of 6	ENSP00000342137.3	Q6ZVX7
	NCCRP1	ENST00000855675.1		c.31G>A	p.Gly11Ser	missense	Exon 1 of 6	ENSP00000525734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383422 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 683218

African (AFR) AF: 0.00 AC: 0 AN: 31274

American (AMR) AF: 0.00 AC: 0 AN: 35936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35564

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080002

Other (OTH) AF: 0.00 AC: 0 AN: 57774

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.072
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.012
Sift	Benign	0.22	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.052	B
Vest4		0.088
MutPred		0.16		Gain of phosphorylation at G11 (P = 0.016)
MVP		0.095
MPC		2.5
ClinPred		0.20	T
GERP RS		-0.48
PromoterAI		-0.012	Neutral
Varity_R		0.059
gMVP		0.087
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: rs1025745434; hg19: chr19-39687653;