10-94338336-T-G

Variant names:

• chr10-94338336-T-G
• rs17109928
• NM_022451.11:c.2091+272A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022451.11(NOC3L):​c.2091+272A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,768 control chromosomes in the GnomAD database, including 1,923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1923 hom., cov: 32)
• Consequence: NOC3L NM_022451.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOC3L	NM_022451.11	c.2091+272A>C		intron_variant	Intron 18 of 20	ENST00000371361.3	NP_071896.8
NOC3L	XR_002957007.2	n.2192+272A>C		intron_variant	Intron 18 of 21
NOC3L	XR_007061982.1	n.2192+272A>C		intron_variant	Intron 18 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOC3L	ENST00000371361.3	c.2091+272A>C		intron_variant	Intron 18 of 20	1	NM_022451.11	ENSP00000360412.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22708 AN: 151652 Hom.: 1918 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22727 AN: 151768 Hom.: 1923 Cov.: 32 AF XY: 0.154 AC XY: 11408 AN XY: 74214

African (AFR) AF: 0.179 AC: 7421 AN: 41396

American (AMR) AF: 0.101 AC: 1546 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1457 AN: 5140

South Asian (SAS) AF: 0.318 AC: 1527 AN: 4806

European-Finnish (FIN) AF: 0.152 AC: 1598 AN: 10546

Middle Eastern (MID) AF: 0.0764 AC: 22 AN: 288

European-Non Finnish (NFE) AF: 0.122 AC: 8298 AN: 67856

Other (OTH) AF: 0.127 AC: 267 AN: 2108

Alfa AF: 0.127 Hom.: 2194

Bravo AF: 0.143

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17109928; hg19: chr10-96098093;