chr21-31924654-C-T

Position:

• chr21-31924654-C-T

Variant summary

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

The NM_014586.2(HUNK):​c.448C>T​(p.His150Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HUNK NM_014586.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50

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]

ACMG classification

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	c.448C>T	p.His150Tyr	missense_variant	2/11	ENST00000270112.7	NP_055401.1
HUNK	XM_011529537.3	c.448C>T	p.His150Tyr	missense_variant	2/10		XP_011527839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUNK	ENST00000270112.7	c.448C>T	p.His150Tyr	missense_variant	2/11	1	NM_014586.2	ENSP00000270112.2
HUNK	ENST00000430354.1	c.103C>T	p.His35Tyr	missense_variant	1/4	3		ENSP00000411860.1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.448C>T (p.H150Y) alteration is located in exon 2 (coding exon 2) of the HUNK gene. This alteration results from a C to T substitution at nucleotide position 448, causing the histidine (H) at amino acid position 150 to be replaced by a tyrosine (Y). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.98	D;.
Vest4		0.57
MutPred		0.69		Loss of disorder (P = 0.0623);.;
MVP		0.33
MPC		2.1
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.41
gMVP		0.88

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: chr21-33296966;