21-31923801-A-G

Variant names:

• chr21-31923801-A-G
• rs11910494
• NM_014586.2:c.262-667A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014586.2(HUNK):​c.262-667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,888 control chromosomes in the GnomAD database, including 14,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (14508 hom., cov: 31)
• Consequence: HUNK NM_014586.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HUNK	NM_014586.2	c.262-667A>G		intron_variant	Intron 1 of 10	ENST00000270112.7	NP_055401.1
HUNK	XM_011529537.3	c.262-667A>G		intron_variant	Intron 1 of 9		XP_011527839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HUNK	ENST00000270112.7	c.262-667A>G		intron_variant	Intron 1 of 10	1	NM_014586.2	ENSP00000270112.2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61407 AN: 151770 Hom.: 14478 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61492 AN: 151888 Hom.: 14508 Cov.: 31 AF XY: 0.402 AC XY: 29867 AN XY: 74248

African (AFR) AF: 0.662 AC: 27397 AN: 41410

American (AMR) AF: 0.272 AC: 4159 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1130 AN: 5148

South Asian (SAS) AF: 0.412 AC: 1980 AN: 4808

European-Finnish (FIN) AF: 0.283 AC: 2990 AN: 10570

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21135 AN: 67892

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.336 Hom.: 39081

Bravo AF: 0.412

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.65
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs11910494; hg19: chr21-33296113;