Variant 21-31873787-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014586.2(HUNK):c.113C>T(p.Pro38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,543,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

HUNK
NM_014586.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.941

Variant links:

Genes affected

HUNK (HGNC:13326): (hormonally up-regulated Neu-associated kinase) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in intracellular signal transduction and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

HUNK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUNK	NM_014586.2 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	1/11	ENST00000270112.7	NP_055401.1
HUNK	XM_011529537.3 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	1/10		XP_011527839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUNK	ENST00000270112.7 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	1/11	1	NM_014586.2	ENSP00000270112	P1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1391816

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

691890

show subpopulations

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:

0.0000148

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

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

Aug 16, 2021

The c.113C>T (p.P38L) alteration is located in exon 1 (coding exon 1) of the HUNK gene. This alteration results from a C to T substitution at nucleotide position 113, causing the proline (P) at amino acid position 38 to be replaced by a leucine (L). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.12

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.96

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

0.96

Vest4

0.37

MutPred

0.52

Gain of catalytic residue at P38 (P = 0.0016);

MVP

0.43

MPC

1.5

ClinPred

0.98

GERP RS

2.9

Varity_R

0.46

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over