chr17-3816241-G-A

Position:

• chr17-3816241-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114118.3(NCBP3):​c.1340C>T​(p.Ser447Leu) 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: 2.67

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10124594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCBP3	NM_001114118.3	c.1340C>T	p.Ser447Leu	missense_variant	11/13	ENST00000389005.6
NCBP3	NM_001398494.1	c.1340C>T	p.Ser447Leu	missense_variant	11/14
NCBP3	XR_007065313.1	n.1363C>T		non_coding_transcript_exon_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCBP3	ENST00000389005.6	c.1340C>T	p.Ser447Leu	missense_variant	11/13	5	NM_001114118.3	P1
NCBP3	ENST00000574911.5	c.*548C>T		3_prime_UTR_variant, NMD_transcript_variant	6/8	1
NCBP3	ENST00000575815.5	n.2057C>T		non_coding_transcript_exon_variant	8/10	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

Mar 14, 2023

The c.1340C>T (p.S447L) alteration is located in exon 11 (coding exon 11) of the NCBP3 gene. This alteration results from a C to T substitution at nucleotide position 1340, causing the serine (S) at amino acid position 447 to be replaced by a leucine (L). 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	0.084
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.052
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.91	D;D
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.078	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.20		Loss of phosphorylation at S447 (P = 0.0368);
MVP		0.043
MPC		0.57
ClinPred		0.66	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr17-3719535;