chr17-3813220-C-T

Variant names:

• chr17-3813220-C-T
• NM_001114118.3:c.1687G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 13/19 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
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

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

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.1687G>A	p.Val563Met	missense	Exon 13 of 13	NP_001107590.1	Q53F19-1
	NCBP3	NM_001398494.1		c.1687G>A	p.Val563Met	missense	Exon 13 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.1687G>A	p.Val563Met	missense	Exon 13 of 13	ENSP00000373657.4	Q53F19-1
	NCBP3	ENST00000574911.5	TSL:1	n.*895G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000467742.1	K7EQA5
	NCBP3	ENST00000574911.5	TSL:1	n.*895G>A		3_prime_UTR	Exon 8 of 8	ENSP00000467742.1	K7EQA5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.52
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.10
Sift	Benign	0.20	T
Sift4G	Benign	0.11	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
PromoterAI		0.0040	Neutral
Varity_R		0.029
gMVP		0.050
Mutation Taster		=88/12	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

hg19: chr17-3716514;