19-39197167-C-T

Variant names:

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

Variant summary

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

The NM_001001414.2(NCCRP1):​c.185C>T​(p.Ala62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000699 in 1,287,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: NCCRP1 NM_001001414.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.585

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

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=0.032689333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCCRP1	NM_001001414.2	c.185C>T	p.Ala62Val	missense_variant	Exon 1 of 6	ENST00000339852.5	NP_001001414.1
NCCRP1	XM_011526906.4	c.185C>T	p.Ala62Val	missense_variant	Exon 1 of 5		XP_011525208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCCRP1	ENST00000339852.5	c.185C>T	p.Ala62Val	missense_variant	Exon 1 of 6	1	NM_001001414.2	ENSP00000342137.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000699 AC: 9 AN: 1287296 Hom.: 0 Cov.: 33 AF XY: 0.00000475 AC XY: 3 AN XY: 631722

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.0000552

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: 0.00000480

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185C>T (p.A62V) alteration is located in exon 1 (coding exon 1) of the NCCRP1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the alanine (A) at amino acid position 62 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.2
DANN	Benign	0.97
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.028
Sift	Benign	0.059	T
Sift4G	Benign	0.25	T
Polyphen		0.029	B
Vest4		0.078
MutPred		0.13		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.040
MPC		1.3
ClinPred		0.36	T
GERP RS		-0.44
Varity_R		0.030
gMVP		0.12

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: rs889943123; hg19: chr19-39687807;