Genetic Variant NM_207363.3:c.580-39725T>C (chr2-132918641-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207363.3(NCKAP5):c.580-39725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,094 control chromosomes in the GnomAD database, including 8,944 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 0.24 ( 8944 hom., cov: 32)

Consequence

NCKAP5
NM_207363.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

8 publications found

Variant links:

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 links:

NCKAP5-AS1 (HGNC:41246): (NCKAP5 antisense RNA 1)

NCKAP5-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_207363.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCKAP5	NM_207363.3	MANE Select	c.580-39725T>C	intron	N/A	NP_997246.2	O14513-1
NCKAP5	NM_207481.4		c.580-39725T>C	intron	N/A	NP_997364.3	O14513-2
NCKAP5-AS1	NR_135572.1		n.95+2990A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.580-39725T>C	intron	N/A	ENSP00000387128.1	O14513-1
NCKAP5-AS1	ENST00000424510.1	TSL:1	n.95+2990A>G	intron	N/A
NCKAP5	ENST00000409213.5	TSL:5	c.580-39725T>C	intron	N/A	ENSP00000386952.1	O14513-2

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36108

AN:

151976

Hom.:

8900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.0989

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0820

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0350

Gnomad OTH

AF:

0.221

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

GnomAD4 genome

AF:

0.238

AC:

36205

AN:

152094

Hom.:

8944

Cov.:

AF XY:

0.239

AC XY:

17743

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.586

AC:

24279

AN:

41440

American (AMR)

AF:

0.338

AC:

5149

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0989

AC:

343

AN:

3468

East Asian (EAS)

AF:

0.467

AC:

2415

AN:

5174

South Asian (SAS)

AF:

0.0522

AC:

252

AN:

4826

European-Finnish (FIN)

AF:

0.0820

AC:

869

AN:

10604

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0350

AC:

2381

AN:

68012

Other (OTH)

AF:

0.219

AC:

463

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

906

1812

2718

3624

4530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.137

Hom.:

8040

Bravo

AF:

0.282

Asia WGS

AF:

0.270

AC:

936

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.7

(source)

DANN

Benign

0.65

PhyloP100

0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over