rs3735231

Positions:

chr7-22976212-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000432176.7(HYCC1):c.624A>G(p.Ser208=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,595,058 control chromosomes in the GnomAD database, including 99,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9511 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90225 hom. )

Consequence

HYCC1
ENST00000432176.7 splice_region, synonymous

Scores

Splicing: ADA: 0.007816

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

HYCC1 (HGNC:24587): (hyccin PI4KA lipid kinase complex subunit 1) The protein encoded by this gene may play a part in the beta-catenin/Lef signaling pathway. Expression of this gene is down-regulated by beta-catenin. Defects in this gene are a cause of hypomyelination with congenital cataract (HCC). [provided by RefSeq, Oct 2008]

HYCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-22976212-T-C is Benign according to our data. Variant chr7-22976212-T-C is described in ClinVar as [Benign]. Clinvar id is 21726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-22976212-T-C is described in Lovd as [Benign]. Variant chr7-22976212-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4 linkuse as main transcript	c.624A>G	p.Ser208=	splice_region_variant, synonymous_variant	7/11	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7 linkuse as main transcript	c.624A>G	p.Ser208=	splice_region_variant, synonymous_variant	7/11	1	NM_032581.4	ENSP00000403396		Q9BYI3-1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53611

AN:

151996

Hom.:

9502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.370

AC:

92045

AN:

248962

Hom.:

17338

AF XY:

0.368

AC XY:

49690

AN XY:

134916

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.351

AC:

506122

AN:

1442944

Hom.:

90225

Cov.:

AF XY:

0.351

AC XY:

252215

AN XY:

718942

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.353

AC:

53654

AN:

152114

Hom.:

9511

Cov.:

AF XY:

0.353

AC XY:

26219

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.352

Hom.:

6392

Bravo

AF:

0.356

Asia WGS

AF:

0.387

AC:

1347

AN:

3478

EpiCase

AF:

0.340

EpiControl

AF:

0.342

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypomyelination and Congenital Cataract

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 02, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0078

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over