8-42943429-C-T

Variant names:

• chr8-42943429-C-T
• rs34112280
• NM_032410.4:c.384C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032410.4(HOOK3):​c.384C>T​(p.Asn128Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,483,608 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (20 hom.)
• Consequence: HOOK3 NM_032410.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.765

Genes affected

HOOK3 (HGNC:23576): (hook microtubule tethering protein 3) 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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 8-42943429-C-T is Benign according to our data. Variant chr8-42943429-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.765 with no splicing effect.
• BS2: High AC in GnomAd4 at 470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOOK3	NM_032410.4	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 5 of 22	ENST00000307602.9	NP_115786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOOK3	ENST00000307602.9	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 5 of 22	1	NM_032410.4	ENSP00000305699.3
HOOK3	ENST00000527306.1	n.570C>T		non_coding_transcript_exon_variant	Exon 5 of 16	1
HOOK3	ENST00000533539.2	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 5 of 23	3		ENSP00000433953.2

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00708

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00493

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00408 AC: 803 AN: 196890 Hom.: 2 AF XY: 0.00421 AC XY: 453 AN XY: 107580

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.000310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000885

Gnomad FIN exome AF: 0.00827

Gnomad NFE exome AF: 0.00606

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00442 AC: 5882 AN: 1331388 Hom.: 20 Cov.: 30 AF XY: 0.00444 AC XY: 2911 AN XY: 655274

Gnomad4 AFR exome AF: 0.000371

Gnomad4 AMR exome AF: 0.000520

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000859

Gnomad4 FIN exome AF: 0.00851

Gnomad4 NFE exome AF: 0.00497

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00294 AC XY: 219 AN XY: 74414

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00708

Gnomad4 NFE AF: 0.00493

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00404 Hom.: 0

Bravo AF: 0.00258

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HOOK3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.8
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs34112280; hg19: chr8-42798572;