rs17517578

Positions:

• chr10-94338616-C-T

Variant summary

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

The ENST00000371361.3(NOC3L):​c.2083G>A​(p.Ala695Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,552,174 control chromosomes in the GnomAD database, including 19,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.14 (1676 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17813 hom.)
• Consequence: NOC3L ENST00000371361.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

Genes affected

NOC3L (HGNC:24034): (NOC3 like DNA replication regulator) Enables RNA binding activity. Predicted to be involved in DNA replication initiation. Predicted to act upstream of or within fat cell differentiation. Located in mitochondrion; nucleolus; and nucleoplasm. [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=0.010573506).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOC3L	NM_022451.11	c.2083G>A	p.Ala695Thr	missense_variant	18/21	ENST00000371361.3	NP_071896.8
NOC3L	XR_002957007.2	n.2184G>A		non_coding_transcript_exon_variant	18/22
NOC3L	XR_007061982.1	n.2184G>A		non_coding_transcript_exon_variant	18/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOC3L	ENST00000371361.3	c.2083G>A	p.Ala695Thr	missense_variant	18/21	1	NM_022451.11	ENSP00000360412	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21588 AN: 152072 Hom.: 1676 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.139 AC: 32759 AN: 235946 Hom.: 2691 AF XY: 0.144 AC XY: 18431 AN XY: 127824

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0779

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.00183

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.154 AC: 215811 AN: 1399984 Hom.: 17813 Cov.: 31 AF XY: 0.156 AC XY: 108118 AN XY: 693510

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0828

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.142 AC: 21584 AN: 152190 Hom.: 1676 Cov.: 32 AF XY: 0.141 AC XY: 10523 AN XY: 74400

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.158

Alfa AF: 0.161 Hom.: 4446

Bravo AF: 0.134

TwinsUK AF: 0.176 AC: 652

ALSPAC AF: 0.151 AC: 582

ESP6500AA AF: 0.112 AC: 493

ESP6500EA AF: 0.160 AC: 1376

ExAC AF: 0.138 AC: 16767

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.67
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.025	N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.066
Sift	Benign	0.39	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.030
MPC		0.071
ClinPred		0.0023	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.20

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: rs17517578; hg19: chr10-96098373; COSMIC: COSV64930897;