chr17-3843109-T-C

Position:

• chr17-3843109-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001114118.3(NCBP3):​c.226A>G​(p.Thr76Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,399,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: NCBP3 NM_001114118.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCBP3	NM_001114118.3	c.226A>G	p.Thr76Ala	missense_variant	2/13	ENST00000389005.6
NCBP3	NM_001398494.1	c.226A>G	p.Thr76Ala	missense_variant	2/14
NCBP3	XR_007065313.1	n.249A>G		non_coding_transcript_exon_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCBP3	ENST00000389005.6	c.226A>G	p.Thr76Ala	missense_variant	2/13	5	NM_001114118.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399352 Hom.: 0 Cov.: 30 AF XY: 0.00000435 AC XY: 3 AN XY: 690190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.226A>G (p.T76A) alteration is located in exon 2 (coding exon 2) of the NCBP3 gene. This alteration results from a A to G substitution at nucleotide position 226, causing the threonine (T) at amino acid position 76 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.15	T
Polyphen		0.63	P
Vest4		0.92
MutPred		0.29		Loss of phosphorylation at T76 (P = 0.0339);
MVP		0.22
MPC		0.82
ClinPred		0.97	D
GERP RS		4.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.25
gMVP		0.79

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: rs1885600031; hg19: chr17-3746403;