17-3813220-C-T

Position:

• chr17-3813220-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114118.3(NCBP3):​c.1687G>A​(p.Val563Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCBP3 NM_001114118.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.522

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056692123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCBP3	NM_001114118.3	c.1687G>A	p.Val563Met	missense_variant	13/13	ENST00000389005.6
NCBP3	NM_001398494.1	c.1687G>A	p.Val563Met	missense_variant	13/14
NCBP3	XR_007065313.1	n.1710G>A		non_coding_transcript_exon_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCBP3	ENST00000389005.6	c.1687G>A	p.Val563Met	missense_variant	13/13	5	NM_001114118.3	P1
NCBP3	ENST00000574911.5	c.*895G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	1
NCBP3	ENST00000576523.1	c.31G>A	p.Val11Met	missense_variant	1/2	2
NCBP3	ENST00000575815.5	n.2404G>A		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 30, 2021

The c.1687G>A (p.V563M) alteration is located in exon 13 (coding exon 13) of the NCBP3 gene. This alteration results from a G to A substitution at nucleotide position 1687, causing the valine (V) at amino acid position 563 to be replaced by a methionine (M). 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	Benign	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0023	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.97	N;N
PROVEAN	Benign	-0.040	N;.
REVEL	Benign	0.10
Sift	Benign	0.20	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.0	B;.
Vest4		0.058
MutPred		0.11		Gain of solvent accessibility (P = 0.0273);.;
MVP		0.043
MPC		0.76
ClinPred		0.13	T
GERP RS		3.6
Varity_R		0.029
gMVP		0.050

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3716514;