rs1049455

chr10-102160718-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004741.5(NOLC1):c.1366T>C(p.Ser456Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,614,018 control chromosomes in the GnomAD database, including 13,463 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (5083 hom., cov: 32)
  • Exomes 𝑓: 0.082 (8380 hom.)
• Consequence: NOLC1 NM_004741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3320317E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOLC1	NM_004741.5	c.1366T>C	p.Ser456Pro	missense_variant	10/13	ENST00000605788.6
NOLC1	NM_001284388.2	c.1396T>C	p.Ser466Pro	missense_variant	10/13
NOLC1	NM_001284389.2	c.1369T>C	p.Ser457Pro	missense_variant	10/13
NOLC1	XM_005270273.3	c.1399T>C	p.Ser467Pro	missense_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOLC1	ENST00000605788.6	c.1366T>C	p.Ser456Pro	missense_variant	10/13	1	NM_004741.5	P4

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28582 AN: 152024 Hom.: 5071 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.0986 AC: 24721 AN: 250828 Hom.: 2640 AF XY: 0.0919 AC XY: 12470 AN XY: 135672

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.0570

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.00256

Gnomad SAS exome AF: 0.0608

Gnomad FIN exome AF: 0.0882

Gnomad NFE exome AF: 0.0809

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0825 AC: 120598 AN: 1461876 Hom.: 8380 Cov.: 33 AF XY: 0.0814 AC XY: 59224 AN XY: 727240

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.0598

Gnomad4 FIN exome AF: 0.0850

Gnomad4 NFE exome AF: 0.0726

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.188 AC: 28623 AN: 152142 Hom.: 5083 Cov.: 32 AF XY: 0.183 AC XY: 13635 AN XY: 74382

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.0915

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.166

Alfa AF: 0.0984 Hom.: 2721

Bravo AF: 0.201

TwinsUK AF: 0.0709 AC: 263

ALSPAC AF: 0.0664 AC: 256

ESP6500AA AF: 0.458 AC: 2015

ESP6500EA AF: 0.0848 AC: 729

ExAC AF: 0.107 AC: 13026

Asia WGS AF: 0.0560 AC: 198 AN: 3478

EpiCase AF: 0.0835

EpiControl AF: 0.0887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	4.1
Dann	Benign	0.54
DEOGEN2	Benign	0.018	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.36	T;T;T
MetaRNN	Benign	0.00023	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.028
MPC		0.046
ClinPred		0.00031	T
GERP RS		-0.49
Varity_R		0.049
gMVP		0.084

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: rs1049455; hg19: chr10-103920475;