10-94344812-T-C

Variant names:

• chr10-94344812-T-C
• rs3758527
• NM_022451.11:c.1470+41A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022451.11(NOC3L):​c.1470+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,443,088 control chromosomes in the GnomAD database, including 59 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 0.0021 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (45 hom.)
• Consequence: NOC3L NM_022451.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 2 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=-0.85).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00213 (324/152304) while in subpopulation EAS AF = 0.055 (285/5186). AF 95% confidence interval is 0.0497. There are 14 homozygotes in GnomAd4. There are 198 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022451.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOC3L	NM_022451.11	MANE Select	c.1470+41A>G		intron	N/A	NP_071896.8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOC3L	ENST00000371361.3	TSL:1 MANE Select	c.1470+41A>G		intron	N/A	ENSP00000360412.3	Q8WTT2
	NOC3L	ENST00000966134.1		c.1470+41A>G		intron	N/A	ENSP00000636193.1
	NOC3L	ENST00000852417.1		c.1470+41A>G		intron	N/A	ENSP00000522476.1

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 326 AN: 152186 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00504 AC: 1048 AN: 207988 AF XY: 0.00473

Gnomad AFR exome AF: 0.000386

Gnomad AMR exome AF: 0.0000862

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0622

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.00184

GnomAD4 exome AF: 0.00182 AC: 2350 AN: 1290784 Hom.: 45 Cov.: 18 AF XY: 0.00175 AC XY: 1134 AN XY: 648068

African (AFR) AF: 0.000106 AC: 3 AN: 28352

American (AMR) AF: 0.0000620 AC: 2 AN: 32240

Ashkenazi Jewish (ASJ) AF: 0.0000445 AC: 1 AN: 22494

East Asian (EAS) AF: 0.0504 AC: 1960 AN: 38894

South Asian (SAS) AF: 0.000844 AC: 64 AN: 75808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5304

European-Non Finnish (NFE) AF: 0.000188 AC: 185 AN: 984900

Other (OTH) AF: 0.00248 AC: 135 AN: 54410

GnomAD4 genome AF: 0.00213 AC: 324 AN: 152304 Hom.: 14 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74480

African (AFR) AF: 0.000313 AC: 13 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0550 AC: 285 AN: 5186

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000493 Hom.: 0

Bravo AF: 0.00278

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.65
PhyloP100		0.51
Mutation Taster		=100/0	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: rs3758527; hg19: chr10-96104569; COSMIC: COSV64929617; COSMIC: COSV64929617;