10-94338336-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 (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/exons	MANE	UniProt
NOC3L	NM_022451.11	c.2091+272A>C		intron_variant		ENST00000371361.3
NOC3L	XR_002957007.2	n.2192+272A>C		intron_variant, non_coding_transcript_variant
NOC3L	XR_007061982.1	n.2192+272A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOC3L	ENST00000371361.3	c.2091+272A>C		intron_variant		1	NM_022451.11	P1

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.127

Alfa AF: 0.128 Hom.: 1754

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17109928; hg19: chr10-96098093;