10-102157062-G-C

Position:

• chr10-102157062-G-C

Variant summary

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

The NM_004741.5(NOLC1):​c.164G>C​(p.Ser55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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=0.23396054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOLC1	NM_004741.5	c.164G>C	p.Ser55Thr	missense_variant	2/13	ENST00000605788.6	NP_004732.2
NOLC1	NM_001284388.2	c.164G>C	p.Ser55Thr	missense_variant	2/13		NP_001271317.1
NOLC1	NM_001284389.2	c.164G>C	p.Ser55Thr	missense_variant	2/13		NP_001271318.1
NOLC1	XM_005270273.3	c.164G>C	p.Ser55Thr	missense_variant	2/13		XP_005270330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOLC1	ENST00000605788.6	c.164G>C	p.Ser55Thr	missense_variant	2/13	1	NM_004741.5	ENSP00000474710.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727248

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.000164

EpiControl AF: 0.00

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

Nov 07, 2022

The c.164G>C (p.S55T) alteration is located in exon 2 (coding exon 2) of the NOLC1 gene. This alteration results from a G to C substitution at nucleotide position 164, causing the serine (S) at amino acid position 55 to be replaced by a threonine (T). 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	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	.;N;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	.;D;.
Sift4G	Benign	0.31	T;T;T
Polyphen		0.68	P;P;P
Vest4		0.22
MutPred		0.29		Loss of disorder (P = 0.0877);Loss of disorder (P = 0.0877);Loss of disorder (P = 0.0877);
MVP		0.37
MPC		0.27
ClinPred		0.81	D
GERP RS		5.9
Varity_R		0.28
gMVP		0.28

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: rs2069608767; hg19: chr10-103916819;