10-102152433-G-A

Position:

• chr10-102152433-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004741.5(NOLC1):​c.23G>A​(p.Arg8His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

Genes affected

NOLC1 (HGNC:15608): (nucleolar and coiled-body phosphoprotein 1) Enables protein heterodimerization activity and protein-macromolecule adaptor activity. Involved in neural crest cell development; neural crest formation; and regulation of translation. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5	c.23G>A	p.Arg8His	missense_variant	1/13	ENST00000605788.6	NP_004732.2
NOLC1	NM_001284388.2	c.23G>A	p.Arg8His	missense_variant	1/13		NP_001271317.1
NOLC1	NM_001284389.2	c.23G>A	p.Arg8His	missense_variant	1/13		NP_001271318.1
NOLC1	XM_005270273.3	c.23G>A	p.Arg8His	missense_variant	1/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6	c.23G>A	p.Arg8His	missense_variant	1/13	1	NM_004741.5	ENSP00000474710.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Oct 12, 2021

The c.23G>A (p.R8H) alteration is located in exon 1 (coding exon 1) of the NOLC1 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the arginine (R) at amino acid position 8 to be replaced by a histidine (H). 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	0.45
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;.;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.1	M;M;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	.;N;.;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.63
MutPred		0.40		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.45
MPC		0.31
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
Varity_R		0.45
gMVP		0.44

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: rs2069520818; hg19: chr10-103912190;