10-102157490-A-T

Position:

• chr10-102157490-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004741.5(NOLC1):​c.376A>T​(p.Ser126Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35776877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5	c.376A>T	p.Ser126Cys	missense_variant	4/13	ENST00000605788.6	NP_004732.2
NOLC1	NM_001284388.2	c.376A>T	p.Ser126Cys	missense_variant	4/13		NP_001271317.1
NOLC1	NM_001284389.2	c.379A>T	p.Ser127Cys	missense_variant	4/13		NP_001271318.1
NOLC1	XM_005270273.3	c.379A>T	p.Ser127Cys	missense_variant	4/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6	c.376A>T	p.Ser126Cys	missense_variant	4/13	1	NM_004741.5	ENSP00000474710.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 31, 2024

The c.376A>T (p.S126C) alteration is located in exon 4 (coding exon 4) of the NOLC1 gene. This alteration results from a A to T substitution at nucleotide position 376, causing the serine (S) at amino acid position 126 to be replaced by a cysteine (C). 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	0.21
BayesDel_addAF	Benign	0.0063	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.0	M;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.4	.;N;.
REVEL	Benign	0.22
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.45
MutPred		0.21		Loss of phosphorylation at S126 (P = 9e-04);Loss of phosphorylation at S126 (P = 9e-04);.;
MVP		0.74
MPC		0.18
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.23

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: chr10-103917247;