10-94353025-C-G

Position:

• chr10-94353025-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022451.11(NOC3L):​c.729G>C​(p.Leu243Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOC3L NM_022451.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0570

Genes affected

NOC3L (HGNC:24034): (NOC3 like DNA replication regulator) Enables RNA binding activity. Predicted to be involved in DNA replication initiation. Predicted to act upstream of or within fat cell differentiation. Located in mitochondrion; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOC3L	NM_022451.11	c.729G>C	p.Leu243Phe	missense_variant	7/21	ENST00000371361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOC3L	ENST00000371361.3	c.729G>C	p.Leu243Phe	missense_variant	7/21	1	NM_022451.11	P1
NOC3L	ENST00000463649.5	n.1581G>C		non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.729G>C (p.L243F) alteration is located in exon 7 (coding exon 7) of the NOC3L gene. This alteration results from a G to C substitution at nucleotide position 729, causing the leucine (L) at amino acid position 243 to be replaced by a phenylalanine (F). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.97	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.012	D
Sift4G	Benign	0.069	T
Polyphen		0.99	D
Vest4		0.69
MutPred		0.65		Loss of disorder (P = 0.1153);
MVP		0.67
MPC		0.43
ClinPred		0.97	D
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr10-96112782;