10-102157452-G-A

Position:

• chr10-102157452-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004741.5(NOLC1):​c.338G>A​(p.Gly113Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000021 (0 hom.)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0190

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087186545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5	c.338G>A	p.Gly113Asp	missense_variant	4/13	ENST00000605788.6	NP_004732.2
NOLC1	NM_001284388.2	c.338G>A	p.Gly113Asp	missense_variant	4/13		NP_001271317.1
NOLC1	NM_001284389.2	c.341G>A	p.Gly114Asp	missense_variant	4/13		NP_001271318.1
NOLC1	XM_005270273.3	c.341G>A	p.Gly114Asp	missense_variant	4/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6	c.338G>A	p.Gly113Asp	missense_variant	4/13	1	NM_004741.5	ENSP00000474710.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Feb 01, 2023

The c.338G>A (p.G113D) alteration is located in exon 4 (coding exon 4) of the NOLC1 gene. This alteration results from a G to A substitution at nucleotide position 338, causing the glycine (G) at amino acid position 113 to be replaced by an aspartic acid (D). 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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.52
DEOGEN2	Benign	0.035	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.16	.;N;.
REVEL	Benign	0.043
Sift	Benign	0.047	.;D;.
Sift4G	Benign	0.34	T;T;T
Polyphen		0.36	B;P;P
Vest4		0.12
MutPred		0.25		Gain of ubiquitination at K118 (P = 0.0259);Gain of ubiquitination at K118 (P = 0.0259);.;
MVP		0.36
MPC		0.18
ClinPred		0.13	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-103917209;