NM_013312.3:c.1633G>A

Variant names:

• chr19-12765697-C-T
• rs190598864
• NM_013312.3:c.1633G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_013312.3(HOOK2):​c.1633G>A​(p.Glu545Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000379 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: HOOK2 NM_013312.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39
• Publications: 4 publications found

Genes affected

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07515058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOOK2	NM_013312.3	MANE Select	c.1633G>A	p.Glu545Lys	missense	Exon 18 of 23	NP_037444.2	Q96ED9-1
	HOOK2	NM_001400041.1		c.1735G>A	p.Glu579Lys	missense	Exon 17 of 22	NP_001386970.1
	HOOK2	NM_001100176.2		c.1627G>A	p.Glu543Lys	missense	Exon 17 of 22	NP_001093646.1	Q96ED9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOOK2	ENST00000397668.8	TSL:1 MANE Select	c.1633G>A	p.Glu545Lys	missense	Exon 18 of 23	ENSP00000380785.2	Q96ED9-1
	HOOK2	ENST00000264827.9	TSL:1	c.1627G>A	p.Glu543Lys	missense	Exon 17 of 22	ENSP00000264827.4	Q96ED9-2
	HOOK2	ENST00000894580.1		c.1921G>A	p.Glu641Lys	missense	Exon 17 of 22	ENSP00000564639.1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000381 AC: 95 AN: 249586 AF XY: 0.000354

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000600

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000369 AC: 539 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.000344 AC XY: 250 AN XY: 727248

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000418 AC: 465 AN: 1112008

Other (OTH) AF: 0.000563 AC: 34 AN: 60396

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74478

African (AFR) AF: 0.000192 AC: 8 AN: 41582

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68032

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000612 Hom.: 0

Bravo AF: 0.000552

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000269 AC: 1

ESP6500EA AF: 0.000732 AC: 6

ExAC AF: 0.000381 AC: 46

EpiCase AF: 0.000600

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.085
Sift	Benign	0.049	D
Sift4G	Benign	0.092	T
Polyphen		0.85	P
Vest4		0.30
MVP		0.53
MPC		0.49
ClinPred		0.052	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.47
gMVP		0.21
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs190598864; hg19: chr19-12876511;