rs10496693

Variant names:

• chr2-132775136-G-A
• rs10496693
• NM_207363.3:c.5050-1242C>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.5050-1242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,092 control chromosomes in the GnomAD database, including 6,181 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 0.28 (6181 hom., cov: 33)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 4 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]

ENSG00000286068 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	NM_207363.3	MANE Select	c.5050-1242C>T		intron	N/A	NP_997246.2
	NCKAP5	NM_207481.4		c.1093-1242C>T		intron	N/A	NP_997364.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.5050-1242C>T		intron	N/A	ENSP00000387128.1
	NCKAP5	ENST00000409213.5	TSL:5	c.1093-1242C>T		intron	N/A	ENSP00000386952.1
	NCKAP5	ENST00000473859.1	TSL:3	n.262+5916C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42267 AN: 151974 Hom.: 6177 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.278 AC: 42298 AN: 152092 Hom.: 6181 Cov.: 33 AF XY: 0.277 AC XY: 20614 AN XY: 74346

African (AFR) AF: 0.324 AC: 13440 AN: 41460

American (AMR) AF: 0.315 AC: 4813 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2151 AN: 5154

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1870 AN: 10602

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16572 AN: 67998

Other (OTH) AF: 0.277 AC: 583 AN: 2106

Alfa AF: 0.262 Hom.: 15696

Bravo AF: 0.295

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.55
PhyloP100		-0.10
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: rs10496693; hg19: chr2-133532709; COSMIC: COSV58431498;