rs16953477

Variant names:

• chr17-3802217-C-G
• rs16953477
• NM_001114118.3:c.*10827G>C

Variant summary

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

The NM_001114118.3(NCBP3):​c.*10827G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,084 control chromosomes in the GnomAD database, including 52 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 0.022 (52 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCBP3 NM_001114118.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 1 publications found

Genes affected

NCBP3 (HGNC:24612): (nuclear cap binding subunit 3) Enables RNA 7-methylguanosine cap binding activity and mRNA binding activity. Involved in defense response to virus. Located in cytoplasm and nuclear speck. [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=-0.82).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0224 (3414/152084) while in subpopulation SAS AF = 0.0258 (124/4804). AF 95% confidence interval is 0.0226. There are 52 homozygotes in GnomAd4. There are 1760 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114118.3. 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
	NCBP3	NM_001114118.3	MANE Select	c.*10827G>C		3_prime_UTR	Exon 13 of 13	NP_001107590.1	Q53F19-1
	NCBP3	NM_001398494.1		c.*10329G>C		3_prime_UTR	Exon 14 of 14	NP_001385423.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCBP3	ENST00000389005.6	TSL:5 MANE Select	c.*10827G>C		3_prime_UTR	Exon 13 of 13	ENSP00000373657.4	Q53F19-1
	NCBP3	ENST00000572988.1	TSL:3	n.466G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3413 AN: 151966 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0224 AC: 3414 AN: 152084 Hom.: 52 Cov.: 33 AF XY: 0.0237 AC XY: 1760 AN XY: 74338

African (AFR) AF: 0.0204 AC: 845 AN: 41508

American (AMR) AF: 0.0132 AC: 201 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0258 AC: 124 AN: 4804

European-Finnish (FIN) AF: 0.0458 AC: 484 AN: 10572

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0236 AC: 1601 AN: 67976

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0215 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.52
DANN	Benign	0.60
PhyloP100		-0.35
Mutation Taster		=99/1	polymorphism

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: rs16953477; hg19: chr17-3705511;