NM_207363.3:c.143+20090C>T

Variant names:

• chr2-133282947-G-A
• rs7577925
• NM_207363.3:c.143+20090C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.143+20090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,950 control chromosomes in the GnomAD database, including 10,207 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10207 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 17 publications found

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

NCKAP5-AS2 (HGNC:54065): (NCKAP5 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.143+20090C>T		intron_variant	Intron 4 of 19	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.143+20090C>T		intron_variant	Intron 4 of 19	5	NM_207363.3	ENSP00000387128.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54779 AN: 151830 Hom.: 10185 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54853 AN: 151950 Hom.: 10207 Cov.: 32 AF XY: 0.359 AC XY: 26645 AN XY: 74304

African (AFR) AF: 0.431 AC: 17855 AN: 41422

American (AMR) AF: 0.318 AC: 4853 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1299 AN: 5164

South Asian (SAS) AF: 0.312 AC: 1498 AN: 4806

European-Finnish (FIN) AF: 0.351 AC: 3710 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23469 AN: 67938

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.347 Hom.: 42825

Bravo AF: 0.363

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs7577925; hg19: chr2-134040519;