Variant chr12-54499463-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005337.5(NCKAP1L):c.211A>G(p.Thr71Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCKAP1L
NM_005337.5 missense, splice_region

Scores

Splicing: ADA: 0.1225

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32

Variant links:

Genes affected

NCKAP1L (HGNC:4862): (NCK associated protein 1 like) This gene encodes a member of the HEM family of tissue-specific transmembrane proteins which are highly conserved from invertebrates through mammals. This gene is only expressed in hematopoietic cells. The encoded protein is a part of the Scar/WAVE complex which plays an important role in regulating cell shape in both metazoans and plants. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

NCKAP1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20650369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP1L	NM_005337.5 linkuse as main transcript	c.211A>G	p.Thr71Ala	missense_variant, splice_region_variant	2/31	ENST00000293373.11
NCKAP1L	NM_001184976.2 linkuse as main transcript	c.61A>G	p.Thr21Ala	missense_variant, splice_region_variant	2/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP1L	ENST00000293373.11 linkuse as main transcript	c.211A>G	p.Thr71Ala	missense_variant, splice_region_variant	2/31	1	NM_005337.5	P1	P55160-1
NCKAP1L	ENST00000545638.2 linkuse as main transcript	c.61A>G	p.Thr21Ala	missense_variant, splice_region_variant	2/31	2			P55160-2
NCKAP1L	ENST00000547500.1 linkuse as main transcript	n.235A>G		splice_region_variant, non_coding_transcript_exon_variant	2/3	2
NCKAP1L	ENST00000548221.5 linkuse as main transcript	c.211A>G	p.Thr71Ala	missense_variant, splice_region_variant, NMD_transcript_variant	2/31	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1386262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693930

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.211A>G (p.T71A) alteration is located in exon 2 (coding exon 2) of the NCKAP1L gene. This alteration results from a A to G substitution at nucleotide position 211, causing the threonine (T) at amino acid position 71 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.0043

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.51

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.16

Sift

Benign

0.12

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.29

B;.

Vest4

0.41

MutPred

0.41

Gain of helix (P = 0.062);.;

MVP

0.11

MPC

0.43

ClinPred

0.91

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.40

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over