17-3816235-T-G

Variant names:

• chr17-3816235-T-G
• rs745508666
• NM_001114118.3:c.1346A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001114118.3(NCBP3):​c.1346A>C​(p.Asn449Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N449S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCBP3 NM_001114118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1346A>C	p.Asn449Thr	missense	Exon 11 of 13	NP_001107590.1	Q53F19-1
	NCBP3	NM_001398494.1		c.1346A>C	p.Asn449Thr	missense	Exon 11 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.1346A>C	p.Asn449Thr	missense	Exon 11 of 13	ENSP00000373657.4	Q53F19-1
	NCBP3	ENST00000574911.5	TSL:1	n.*554A>C		non_coding_transcript_exon	Exon 6 of 8	ENSP00000467742.1	K7EQA5
	NCBP3	ENST00000574911.5	TSL:1	n.*554A>C		3_prime_UTR	Exon 6 of 8	ENSP00000467742.1	K7EQA5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251406 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0038	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.60	T
PhyloP100		4.2
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.079
Sift	Benign	0.037	D
Sift4G	Benign	0.57	T
Polyphen		0.99	D
Vest4		0.64
MutPred		0.17		Gain of glycosylation at N449 (P = 0.036)
MVP		0.043
MPC		1.6
ClinPred		0.69	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.14

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: rs745508666; hg19: chr17-3719529;