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GeneBe

21-31924757-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014586.2(HUNK):c.551A>T(p.His184Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HUNK
NM_014586.2 missense

Scores

14
3
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.91
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HUNKNM_014586.2 linkuse as main transcriptc.551A>T p.His184Leu missense_variant 2/11 ENST00000270112.7
HUNKXM_011529537.3 linkuse as main transcriptc.551A>T p.His184Leu missense_variant 2/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HUNKENST00000270112.7 linkuse as main transcriptc.551A>T p.His184Leu missense_variant 2/111 NM_014586.2 P1
HUNKENST00000430354.1 linkuse as main transcriptc.206A>T p.His69Leu missense_variant 1/43

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsOct 27, 2022The c.551A>T (p.H184L) alteration is located in exon 2 (coding exon 2) of the HUNK gene. This alteration results from a A to T substitution at nucleotide position 551, causing the histidine (H) at amino acid position 184 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
0.99
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
Cadd
Pathogenic
27
Dann
Benign
0.97
DEOGEN2
Uncertain
0.49
T;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.49
D
MutationAssessor
Pathogenic
4.0
H;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-10
D;D
REVEL
Pathogenic
0.84
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.97
MutPred
0.93
Gain of ubiquitination at K188 (P = 0.0941);.;
MVP
0.91
MPC
2.2
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.91
gMVP
0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-33297069; API