NM_207363.3:c.5356G>A

Variant names:

• chr2-132731824-C-T
• rs765563733
• NM_207363.3:c.5356G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_207363.3(NCKAP5):​c.5356G>A​(p.Ala1786Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1786V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: NCKAP5 NM_207363.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.733
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024775535).
• BP6: Variant 2-132731824-C-T is Benign according to our data. Variant chr2-132731824-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3182812.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	NM_207363.3	MANE Select	c.5356G>A	p.Ala1786Thr	missense	Exon 17 of 20	NP_997246.2	O14513-1
	NCKAP5	NM_207481.4		c.1399G>A	p.Ala467Thr	missense	Exon 15 of 18	NP_997364.3	O14513-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.5356G>A	p.Ala1786Thr	missense	Exon 17 of 20	ENSP00000387128.1	O14513-1
	NCKAP5	ENST00000409213.5	TSL:5	c.1399G>A	p.Ala467Thr	missense	Exon 15 of 18	ENSP00000386952.1	O14513-2
	NCKAP5	ENST00000640590.1	TSL:5	c.226G>A	p.Ala76Thr	missense	Exon 1 of 3	ENSP00000490966.1	A0A1W2PNT1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 248886 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461686 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.021
DANN	Benign	0.86
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-0.73
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.065
Sift	Benign	0.60	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.022
MutPred		0.12		Gain of phosphorylation at A1786 (P = 0.0235)
MVP		0.19
MPC		0.039
ClinPred		0.024	T
GERP RS		-5.3
PromoterAI		-0.045	Neutral
Varity_R		0.027
gMVP		0.12
Mutation Taster		=97/3	polymorphism

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: rs765563733; hg19: chr2-133489397; COSMIC: COSV58425437; COSMIC: COSV58425437;