rs1049455

Variant names:

• chr10-102160718-T-C
• rs1049455
• NM_004741.5:c.1366T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004741.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOLC1	NM_004741.5	MANE Select	c.1366T>C	p.Ser456Pro	missense	Exon 10 of 13	NP_004732.2
	NOLC1	NM_001284388.2		c.1396T>C	p.Ser466Pro	missense	Exon 10 of 13	NP_001271317.1
	NOLC1	NM_001284389.2		c.1369T>C	p.Ser457Pro	missense	Exon 10 of 13	NP_001271318.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOLC1	ENST00000605788.6	TSL:1 MANE Select	c.1366T>C	p.Ser456Pro	missense	Exon 10 of 13	ENSP00000474710.2
	NOLC1	ENST00000405356.5	TSL:1	c.1396T>C	p.Ser466Pro	missense	Exon 10 of 13	ENSP00000385410.1
	NOLC1	ENST00000370007.5	TSL:1	c.1390T>C	p.Ser464Pro	missense	Exon 10 of 13	ENSP00000359024.5

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

GnomAD2 exomes AF: 0.0986 AC: 24721 AN: 250828 AF XY: 0.0919

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 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

African (AFR) AF: 0.489 AC: 16368 AN: 33480

American (AMR) AF: 0.0618 AC: 2762 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3611 AN: 26136

East Asian (EAS) AF: 0.00146 AC: 58 AN: 39700

South Asian (SAS) AF: 0.0598 AC: 5158 AN: 86258

European-Finnish (FIN) AF: 0.0850 AC: 4542 AN: 53414

Middle Eastern (MID) AF: 0.148 AC: 853 AN: 5768

European-Non Finnish (NFE) AF: 0.0726 AC: 80744 AN: 1112002

Other (OTH) AF: 0.108 AC: 6502 AN: 60396

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

African (AFR) AF: 0.475 AC: 19720 AN: 41494

American (AMR) AF: 0.0953 AC: 1456 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3468

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5166

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4822

European-Finnish (FIN) AF: 0.0915 AC: 969 AN: 10588

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5253 AN: 68008

Other (OTH) AF: 0.166 AC: 350 AN: 2112

Alfa AF: 0.118 Hom.: 6157

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 v4.9

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
MetaRNN	Benign	0.00023	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.41
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.055
Sift	Benign	0.34	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.046
ClinPred		0.00031	T
GERP RS		-0.49
Varity_R		0.049
gMVP		0.084
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1049455; hg19: chr10-103920475;